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Wang, Li, Zhenhong Chen, Li An, Yajuan Wang, Zhijian Zhang, Yinghua Guo, and Changting Liu. "Analysis of Long Non-Coding RNA Expression Profiles in Non-Small Cell Lung Cancer." Cellular Physiology and Biochemistry 38, no. 6 (2016): 2389–400. http://dx.doi.org/10.1159/000445591.
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Background/Aims: Long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. However, the role of lncRNA expression in human Non-small cell lung cancer (NSCLC) biology, prognosis and molecular classification remains unknown. Methods: We established the IncRNA profile in NSCLC by re-annotation of microarrays from the Gene expression omnibus database. Quantitative real-time PCR was used to determine expression of LINC00342. Results: 6066 differentially expressed IncRNAs were identified and we found a novel IncRNA, LINC00342 was significantly up-regulated in NSCLC tissues compared with normal tissues. We confirmed the over-expression of LINC00342 in a cohort of NSCLC patients and found LINC00342 expression level was positively correlated with lymph node metastasis and TNM stages. Furthermore, in a large online database of 1942 NSCLC patients, high expression of LINC00342 indicated poor Overall survival (HR = 1.28, 95% CI: 1.13-1.45) and post progression survival (HR = 1.43, 95% CI: 1.09-1.88). Bioinformatics analyses showed that LINC00342 was co-expressed with different protein-coding genes in NSCLC and normal tissues. Additionally, gene set enrichment analyses found that PTEN and P53 pathways genes were enriched in the groups with higher LINC00342 expression level. By small interfering RNAs mediated silence of LINC00342, proliferation ability was significantly inhibited in lung cancer cell line. Conclusion: To summary, our findings indicate that a set of IncRNAs are differentially expressed in NSCLC and we characterized a novel IncRNA, LINC00342 which is significantly up-regulated in NSCLC and could be a prognostic biomarker.
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Rothzerg, Emel, Xuan Dung Ho, Jiake Xu, David Wood, Aare Märtson, and Sulev Kõks. "Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma." Genes 12, no. 8 (July 26, 2021): 1132. http://dx.doi.org/10.3390/genes12081132.
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The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.
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Zong, Zhen, Hui Li, Zhuo-Min Yu, Fu-Xin Tang, Xiao-Jian Zhu, Hua-Kai Tian, Tai-Cheng Zhou, and He Wang. "Prognostic thirteen-long non-coding RNAs (IncRNAs) could improve the survival prediction of gastric cancer." Gastroenterología y Hepatología 43, no. 10 (December 2020): 598–606. http://dx.doi.org/10.1016/j.gastrohep.2020.01.016.
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Zong, Zhen, Hui Li, Zhuo-Min Yu, Fu-Xin Tang, Xiao-Jian Zhu, Hua-Kai Tian, Tai-Cheng Zhou, and He Wang. "Prognostic thirteen-long non-coding RNAs (IncRNAs) could improve the survival prediction of gastric cancer." Gastroenterología y Hepatología (English Edition) 43, no. 10 (December 2020): 598–606. http://dx.doi.org/10.1016/j.gastre.2020.01.019.
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Butova, Romana, Petra Vychytilova-Faltejskova, Adela Souckova, Sabina Sevcikova, and Roman Hajek. "Long Non-Coding RNAs in Multiple Myeloma." Non-Coding RNA 5, no. 1 (January 24, 2019): 13. http://dx.doi.org/10.3390/ncrna5010013.
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Multiple myeloma (MM) is the second most common hematooncological disease of malignant plasma cells in the bone marrow. While new treatment brought unprecedented increase of survival of patients, MM pathogenesis is yet to be clarified. Increasing evidence of expression of long non-coding RNA molecules (lncRNA) linked to development and progression of many tumors suggested their important role in tumorigenesis. To date, over 15,000 lncRNA molecules characterized by diversity of function and specificity of cell distribution were identified in the human genome. Due to their involvement in proliferation, apoptosis, metabolism, and differentiation, they have a key role in the biological processes and pathogenesis of many diseases, including MM. This review summarizes current knowledge of non-coding RNAs (ncRNA), especially lncRNAs, and their role in MM pathogenesis. Undeniable involvement of lncRNAs in MM development suggests their potential as biomarkers.
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Levakov, S. A., G. Ya Azadova, A. E. Mamedova, Kh R. Movtaeva, M. I. Maslyakova, M. S. Pavlyukov, M. I. Shakhparonov, and N. V. Antipova. "Expression of long non-coding RNAs ROR and MALAT1 in uterine fibroids." Voprosy ginekologii, akušerstva i perinatologii 20, no. 4 (2021): 17–21. http://dx.doi.org/10.20953/1726-1678-2021-4-17-21.
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Objective. To study the expression level of long non-coding RNAs ROR and MALAT1 in tissue samples of uterine fibroids. Patients and methods. Samples of myomatous nodes and tissues of normal myometrium in 28 women of reproductive age were examined. The analysis of the expression of long non-coding RNAs was carried out using a real-time reverse-transcription polymerase chain reaction (RT-PCR) with specific primers. Results. There was a significant decrease in the expression level of long non-coding RNA ROR and an increase in the MALAT1 expression in tissue samples of uterine fibroids relative to the control group. Conclusion. The results obtained demonstrate a possible role of long non-coding RNAs in the development of uterine fibroids and correlate with the data which we obtained for patients with endometriosis. Detecting the expression level of long non-coding RNAs can improve the existing methods for diagnosing this disease. However, further research is required to determine the clinical significance of MALAT1 and ROR, and the molecular mechanisms underlying the action of these RNAs in uterine fibroid cells. Key words: long non-coding RNAs, uterine fibroids, myomectomy, lncROR, MALAT1
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Dhingra, Sourabh. "Role of Non-coding RNAs in Fungal Pathogenesis and Antifungal Drug Responses." Current Clinical Microbiology Reports 7, no. 4 (October 2, 2020): 133–41. http://dx.doi.org/10.1007/s40588-020-00151-7.
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Abstract Purpose of Review Non-coding RNAs (ncRNAs), including regulatory small RNAs (sRNAs) and long non-coding RNAs (lncRNAs), constitute a significant part of eukaryotic genomes; however, their roles in fungi are just starting to emerge. ncRNAs have been shown to regulate gene expression in response to varying environmental conditions (like stress) and response to chemicals, including antifungal drugs. In this review, I highlighted recent studies focusing on the functional roles of ncRNAs in pathogenic fungi. Recent Findings Emerging evidence suggests sRNAs (small RNAs) and lncRNAs (long non-coding RNAs) play an important role in fungal pathogenesis and antifungal drug response. Their roles include posttranscriptional gene silencing, histone modification, and chromatin remodeling. Fungal pathogens utilize RNA interference (RNAi) mechanisms to regulate pathogenesis-related genes and can also transfer sRNAs inside the host to suppress host immunity genes to increase virulence. Hosts can also transfer sRNAs to induce RNAi in fungal pathogens to reduce virulence. Additionally, sRNAs and lncRNAs also regulate gene expression in response to antifungal drugs increasing resistance (and possibly tolerance) to drugs. Summary Herein, I discuss what is known about ncRNAs in fungal pathogenesis and antifungal drug responses. Advancements in genomic technologies will help identify the ncRNA repertoire in fungal pathogens, and functional studies will elucidate their mechanisms. This will advance our understanding of host-fungal interactions and potentially help develop better treatment strategies.
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Zhang, Zhuo, Sophia Shi, Jingxia Li, and Max Costa. "Long Non-Coding RNA MEG3 in Metal Carcinogenesis." Toxics 11, no. 2 (February 7, 2023): 157. http://dx.doi.org/10.3390/toxics11020157.
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Most transcripts from human genomes are non-coding RNAs (ncRNAs) that are not translated into proteins. ncRNAs are divided into long (lncRNAs) and small non-coding RNAs (sncRNAs). LncRNAs regulate their target genes both transcriptionally and post-transcriptionally through interactions with proteins, RNAs, and DNAs. Maternally expressed gene 3 (MEG3), a lncRNA, functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Among them, lung cancer is the one that can be induced by exposure to all of these metals. In vitro studies have demonstrated that the chronic exposure of normal human bronchial epithelial cells (BEAS-2B) to these metals can cause malignant cell transformation. Metal-transformed cells have the capability to cause an increase in cell proliferation, resistance to apoptosis, elevated migration and invasion, and properties of cancer stem-like cells. Studies have revealed that MEG is downregulated in Cr(VI)-transformed cells, nickel-transformed cells, and cadmium (Cd)-transformed cells. The forced expression of MEG3 reduces the migration and invasion of Cr(VI)-transformed cells through the downregulation of the neuronal precursor of developmentally downregulated protein 9 (NEDD9). MEG3 suppresses the malignant cell transformation of nickel-transformed cells. The overexpression of MEG3 decreases Bcl-xL, causing reduced apoptosis resistance in Cd-transformed cells. This paper reviews the current knowledge of lncRNA MEG3 in metal carcinogenesis.
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Dragomir, Mihnea Paul, Scott Kopetz, Jaffer A. Ajani, and George Adrian Calin. "Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility." Gut 69, no. 4 (February 7, 2020): 748–63. http://dx.doi.org/10.1136/gutjnl-2019-318279.
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One of the most unexpected discoveries in molecular oncology, in the last decades, was the identification of a new layer of protein coding gene regulation by transcripts that do not codify for proteins, the non-coding RNAs. These represent a heterogeneous category of transcripts that interact with many types of genetic elements, including regulatory DNAs, coding and other non-coding transcripts and directly to proteins. The final outcome, in the malignant context, is the regulation of any of the cancer hallmarks. Non-coding RNAs represent the most abundant type of hormones that contribute significantly to cell-to cell communication, revealing a complex interplay between tumour cells, tumour microenvironment cells and immune cells. Consequently, profiling their abundance in bodily fluids became a mainstream of biomarker identification. Therapeutic targeting of non-coding RNAs represents a new option for clinicians that is currently under development. This review will present the biology and translational value of three of the most studied categories on non-coding RNAs, the microRNAs, the long non-coding RNAs and the circular RNAs. We will also focus on some aspirational concepts that can help in the development of clinical applications related to non-coding RNAs, including using pyknons to discover new non-coding RNAs, targeting human-specific transcripts which are expressed specifically in the tumour cell and using non-coding RNAs to increase the efficiency of immunotherapy.
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Chaabane, Mohamed, Robert M. Williams, Austin T. Stephens, and Juw Won Park. "circDeep: deep learning approach for circular RNA classification from other long non-coding RNA." Bioinformatics 36, no. 1 (July 3, 2019): 73–80. http://dx.doi.org/10.1093/bioinformatics/btz537.
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Abstract Motivation Over the past two decades, a circular form of RNA (circular RNA), produced through alternative splicing, has become the focus of scientific studies due to its major role as a microRNA (miRNA) activity modulator and its association with various diseases including cancer. Therefore, the detection of circular RNAs is vital to understanding their biogenesis and purpose. Prediction of circular RNA can be achieved in three steps: distinguishing non-coding RNAs from protein coding gene transcripts, separating short and long non-coding RNAs and predicting circular RNAs from other long non-coding RNAs (lncRNAs). However, the available tools are less than 80 percent accurate for distinguishing circular RNAs from other lncRNAs due to difficulty of classification. Therefore, the availability of a more accurate and fast machine learning method for the identification of circular RNAs, which considers the specific features of circular RNA, is essential to the development of systematic annotation. Results Here we present an End-to-End deep learning framework, circDeep, to classify circular RNA from other lncRNA. circDeep fuses an RCM descriptor, ACNN-BLSTM sequence descriptor and a conservation descriptor into high level abstraction descriptors, where the shared representations across different modalities are integrated. The experiments show that circDeep is not only faster than existing tools but also performs at an unprecedented level of accuracy by achieving a 12 percent increase in accuracy over the other tools. Availability and implementation https://github.com/UofLBioinformatics/circDeep. Supplementary information Supplementary data are available at Bioinformatics online.
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Лукина, С. С., А. М. Бурденный, Е. А. Филиппова, И. В. Пронина, Н. А. Иванова, Т. П. Казубская, Э. А. Брага, and В. И. Логинов. "The role of long non-coding RNA and DNA methylation in the pathogenesis of ovarian cancer." Zhurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia», no. 4 (December 12, 2022): 143–56. http://dx.doi.org/10.25557/0031-2991.2022.04.143-156.
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Рак яичников (РЯ) представляет собой группу агрессивных гетерогенных злокачественных опухолей, характеризующихся быстрой прогрессией, низким диагностическим потенциалом, высокой частотой неблагоприятных исходов и высоким потенциалом метастазирования. В обзоре авторы концентрируют внимание на одном из основных регуляторов клеточных процессов, приводящем к образованию опухолей, а именно на длинных некодирующих РНК (днРНК). Известно, что они участвуют в регуляции экспрессии генов на транскрипционном, пост-транскрипционном, трансляционном и пост-трансляционном уровнях, оказывая влияние на такие фундаментальные биологические процессы, как дифференцировка, пролиферация, дозовая компенсация генов, ремоделирование хроматина, геномный импринтинг, альтернативный сплайсинг прем РНК и другие. Они могут выступать как в роли онкогенов, так и в роли генов-супрессоров опухолей. Многочисленные данные показывают, что днРНК вовлечены в патогенез рака яичников, а их аберрантное метилирование представляет один из эпигенетических механизмов регуляции их собственной экспрессии. цель обзора изучение вклада днРНК и ДНК-метилирования в процессы онкогенеза рака яичников и их потенциала в качестве биомаркеров. Особое внимание уделено применению экзосомальных днРНК в неинвазивной диагностике рака яичников.методика. Проведен анализ литературы по международным базам Scopus, Web of science по ключевым словам: рак яичников, длинные некодирующие РНК, ДНК-метилирование. В соответствии с целью обзора предложены и утверждены части, раскрывающие потенциал нкРНК в патогенезе РЯ. Заключение. Изучение свойств днРНК и ДНК-метилирования - путь к улучшению прогноза заболевания, общей выживаемости и качества жизни пациенток с РЯ, к появлению принципиально новых биомаркеров для ранней диагностики, разработки таргетной терапии и персонализированному лечению этого социально значимого заболевания. Background. Ovarian cancer (OC) is a group of aggressive heterogeneous malignant neoplasms characterized by rapid progression, low diagnostic potential, high incidence of adverse outcomes, and high potential for metastasis. The present review focuses on one of the main regulators of cell processes that lead to the formation of tumors, namely, long non-coding RNAs (lncRNAs). It is known that they are involved in the regulation of gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels, thereby influencing fundamental biological processes, such as differentiation, proliferation, dose compensation of genes, chromatin remodeling, genomic imprinting, alternative pre-mRNA splicing, and others. lncRNAs can act both as oncogenes and as tumor suppressor genes. Multiple reports show that lncRNAs are involved in the pathogenesis of OC, and their aberrant methylation is one of the most important epigenetic mechanisms for regulation of their own expression.the aim of this review is to address the contribution of IncRNAs and DNA methylation to the oncogenesis of OC and the lncRNA potential as biomarkers. Special attention is paid to the use of exosomal lncRNAs in non-invasive diagnostics of OC.methods. The search for literature was performed in the Scopus and Web of Science databases using the following keywords: ovarian cancer, long non-coding RNAs, DNA methylation. In accordance with the objectives of the review, the parts that addressed the role of IncRNAs in the pathogenesis of OC were proposed and approved. All articles used in the review were obtained from open sources.conclusion. Studying IncRNA properties and DNA methylation will improve the prognosis, overall survival, and quality of life of patients with OC. Such studies will help developing fundamentally new biomarkers, targeted therapy and personalized treatment of this socially significant disease.
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Li, Hongjuan, Yaqin Chen, Chunyan Wu, Haiyan Zhao, Xuesong Zhang, and Caidi Zhu. "Downregulation of long noncoding RNA T1NCR inhibits cell proliferation, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma." Tobacco Regulatory Science 7, no. 6 (November 3, 2021): 6499–510. http://dx.doi.org/10.18001/trs.7.6.125.
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Accumulating reports have identified that long non-coding RNAs (IncRNAs) function as key regulators of tumor initiation and progression. The aim of the current study was to determine the clinical significance and functional role of TINCR in hepatocellular carcinoma (HCC). In the present study, the level of IncRNA TINCR expression was significantly upregulated in HCC tissues compared to adjacent normal tissues. Higher levels of IncRNA TINCR expression were significantly correlated with tumor size and vascular invasion of HCC patients. LncRNA TINCR knockdown inhibited cell proliferation ability, increased the proportion of G1 phase cells, reduced the proportion of S phase cells, and suppressed cell invasion of HCC in vitro. Additionally, IncRNA TINCR knockdown inhibited the HCC cell epithelial-mesenchymal transition (EMT) phenomenon by upregulating E-cadherin and reducing N-cadherin expression. We demonstrated that knockdown of IncRNA reduced tumor growth in vivo. Thus, these results indicated that IncRNA TINCR exhibits a tumor oncogenic role in HCC and inhibition of IncRNA TINCR might serve as a therapeutic target for HCC.
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Singh, Ajeet, A. T. Vivek, and Shailesh Kumar. "AlnC: An extensive database of long non-coding RNAs in angiosperms." PLOS ONE 16, no. 4 (April 14, 2021): e0247215. http://dx.doi.org/10.1371/journal.pone.0247215.
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Long non-coding RNAs (lncRNAs) are defined as transcripts of greater than 200 nucleotides that play a crucial role in various cellular processes such as the development, differentiation and gene regulation across all eukaryotes, including plant cells. Since the last decade, there has been a significant rise in our understanding of lncRNA molecular functions in plants, resulting in an exponential increase in lncRNA transcripts, while these went unannounced from the major Angiosperm plant species despite the availability of large-scale high throughput sequencing data in public repositories. We, therefore, developed a user-friendly, open-access web interface, AlnC (Angiosperm lncRNA Catalogue) for the exploration of lncRNAs in diverse Angiosperm plant species using recent 1000 plant (1KP) trancriptomes data. The current version of AlnC offers 10,855,598 annotated lncRNA transcripts across 682 Angiosperm plant species encompassing 809 tissues. To improve the user interface, we added features for browsing, searching, and downloading lncRNA data, interactive graphs, and an online BLAST service. Additionally, each lncRNA record is annotated with possible small open reading frames (sORFs) to facilitate the study of peptides encoded within lncRNAs. With this user-friendly interface, we anticipate that AlnC will provide a rich source of lncRNAs for small-and large-scale studies in a variety of flowering plants, as well as aid in the improvement of key characteristics in relevance to their economic importance. Database URL: http://www.nipgr.ac.in/AlnC
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Hu, Guangzhen, Asha Nair, Tammy Price-Troska, Eric D. Wieben, and Mamta Gupta. "Mantle Cell Lymphoma Associated Long Non-Coding RNAs Regulate Polycomb Repressive Complex-2." Blood 124, no. 21 (December 6, 2014): 140. http://dx.doi.org/10.1182/blood.v124.21.140.140.
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Abstract Long non-coding RNAs (lncRNA) are key regulatory RNAs that do not code for protein. Recently lncRNAs have been recognized as key regulators of gene expression and chromatin organization. Although, deregulation of lncRNAs such as HOTAIR, MALAT1 and H19 has been reported in solid cancers, role of lncRNAs in lymphoma or other hematologic malignancies is not known. The aim of this study is to identify lymphoma-associated lncRNAs and elucidate their role in disease pathogenesis. Next generation RNA-sequencing and validation studies were carried out on mantle cell lymphoma (MCL) patient samples along with normal controls. As a result, hundreds of lncRNAs were found overexpressed in the MCL samples as compared with normal B cells, including RP11-24J23.2 (50 fold), RP11-12A2.3 (36 fold) and DLEU7-AS1 (19 fold). Quantitative RT-PCR (QRT-PCR) confirmed higher expression of RP11-24J23.2, RP11-12A2.3, and DLEU7-AS1 in MCL patient samples as compared to normal B cells. To investigate the biological significance of lncRNAs in MCL cells, we overexpressed RP11-24J23.2, RP11-12A2.3, and DLEU7-AS1 lncRNAs and analyzed effects on cell proliferation and apoptosis. To achieve overexpression lncRNAs, RP11-24J23.2, RP11-12A2.3, and DLEU7-AS1 were cloned individually in expression pcDNA3.1 generating constructs: pcDNA3RP11-24J23.2, pcDNA3RP11-12A2.3 and pcDNA3DLEU7-AS1and then transfected into MCL cell lines along with pcDNA3.1. QRT-PCR revealed effective overexpression (~100 fold increase over baseline) for each transfected lncRNAs construct in Granta and Mino cells. Analysis of proliferation and survival showed that overexpressing RP11-24J23.2, RP11-12A2.3 or DLEU7-AS1 promotes cell proliferation and survival in these cells as compared to the vector controls. Most of the lncRNAs found so far have been linked to the transcriptional regulation of the target genes through their association with chromatin remodeling factors such as Polycomb Repressive Complex 2 (PRC2). To identify the functional relevance of RP11-24J23.2, RP11-12A2.3, and DLEU7-AS1 lncRNAs, we examined the binding of the lymphoma specific lncRNAs with PRC2 complex, by performing RNA immunoprecipitation (RNA-IP) using specific antibodies to EZH2, EED and SUZ12. The RNA-IP results demonstrate high affinity binding of all three lncRNAs with SUZ12 and EED but a weak binding with EZH2. Furthermore, RNA-IP using antibody to histone 3-lysine 27 trimethylation (H3K27me3), a suppressive histone mark associated with PRC2 complex, also showed efficient binding with RP11-24J23.2, RP11-12A2.3, and DLEU7-AS1. These results suggest that RP11-24J23.2, RP11-12A2.3, and DLEU7-AS1 lncRNAs can directly associated with PRC2 complex at chromatin. To understand the mechanism of increased cell growth after overexpression of lncRNAs, RP11-24J23.2, RP11-12A2.3 or DLEU7-AS1, we analyzed expression level of important genes signature of MCL pathogenesis that include cyclin D1, cyclin D3, c-Myc, P14, and SOX11, a member of the group C SOX (SRY-related HMG-box) transcription factor family. Our results demonstrate that overexpression of lncRNAs RP11-24J23.2, RP11-12A2.3 or DLEU7-AS1 enhanced the levels of cyclin D1 (>2 fold) mRNA without any impact on cyclin D3 or c-Myc transcript levels. In contrast overexpression of RP11-24J23.2, RP11-12A2.3 or DLEU7-AS1 lncRNAs decreased SOX11 (0.08, 0.1 and 0.06 respectively) and P14 (0.06, 0.7 and 0.40 respectively) mRNA expression in Mino cells. To gain understanding of the mechanism involved in the suppression of SOX11 by the lncRNAs, we performed Chromatin immunoprecipitation assays with EZH2, EED and SUZ12 antibodies on Mino cells transfected with pcDNA3RP11-24J23.2, pcDNA3RP11-12A2.3 and pcDNA3DLEU7-AS1 or vector control. The data showed that overexpression of RP11-12A2.3 and DLEU7-AS1 significantly increased the binding of EED and to a lesser extent of EZH2 to SOX11 promoter while the binding of SUZ12 to SOX11 promoter was not changed as compared to vector alone. In conclusion, our results imply that lncRNAs are overexpressed in the MCL. Moreover, lymphoma associated lncRNAs (RP11-24J23.2, RP11-12A2.3 and DLEU7-AS1) regulate SOX11 expression via PRC2 complex contributing towards growth of MCL cells. Specific nature of lncRNAs found in lymphoma samples suggests that lncRNAs can be used as potential biomarkers for mantle cell lymphoma. Disclosures No relevant conflicts of interest to declare.
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Gong, Xue, Gengze Wu, and Chunyu Zeng. "Role of circular RNAs in cardiovascular diseases." Experimental Biology and Medicine 244, no. 2 (January 17, 2019): 73–82. http://dx.doi.org/10.1177/1535370218822988.
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Over the last several decades, cardiovascular diseases largely increase the morbidity and mortality especially in developed countries, affecting millions of people worldwide. Although extensive work over the last two decades attempted to decipher the molecular network of regulating the pathogenesis and progression of these diseases, evidences from clinical trials with newly revealed targets failed to show more evidently salutary effects, indicating the inefficiency of understanding the complete regulatory landscape. Recent studies have shifted their focus from coding genes to the non-coding ones, which consist of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the lately re-discovered a unique group of RNAs—circular RNAs (circRNAs). As the focus now has been shifted to the newly identified group of non-coding RNAs, circRNAs exhibit stability, highly conservation and relative enriched expression abundance in some cases, which are distinct from their cognate linear counterparts—lncRNAs. So far, emerging evidence begins to support the critical role of circRNAs in organogenesis and pathogenesis as exemplified in the central nervous system, and could be just as implicative in the cardiovascular system, suggesting a therapeutic perspective in related diseases. Impact statement Circular RNAs are important regulators of multiple biological processes such as organogenesis and oncogenesis. Although the bulk of concerning studies focused on revealing their diversified roles in various types of cancers, reports began to accumulate in cardiovascular field these days. We summarize circular RNAs implicated in cardiovascular diseases, aiming to highlight the advances in the knowledge of such diseases and their potential of being promising target for diagnosis and therapy.
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Luykx, Giuliani, Giuliani, and Veldink. "Coding and Non-Coding RNA Abnormalities in Bipolar Disorder." Genes 10, no. 11 (November 19, 2019): 946. http://dx.doi.org/10.3390/genes10110946.
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The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.
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Yang, Yalan, Rong Zhou, Shiyun Zhu, Xunbi Li, Hua Li, Hui Yu, and Kui Li. "Systematic Identification and Molecular Characteristics of Long Noncoding RNAs in Pig Tissues." BioMed Research International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/6152582.
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Long noncoding RNAs (lncRNAs) are non-protein-coding RNAs that are involved in a variety of biological processes. The pig is an important farm animal and an ideal biomedical model. In this study, we performed a genome-wide scan for lncRNAs in multiple tissue types from pigs. A total of 118 million paired-end 90 nt clean reads were obtained via strand-specific RNA sequencing, 80.4% of which were aligned to the pig reference genome. We developed a stringent bioinformatics pipeline to identify 2,139 high-quality multiexonic lncRNAs. The characteristic analysis revealed that the novel lncRNAs showed relatively shorter transcript length, fewer exons, and lower expression levels in comparison with protein-coding genes (PCGs). The guanine-cytosine (GC) content of the protein-coding exons and introns was significantly higher than that of the lncRNAs. Moreover, the single nucleotide polymorphism (SNP) density of lncRNAs was significantly higher than that of PCGs. Conservation analysis revealed that most lncRNAs were evolutionarily conserved among pigs, humans, and mice, such as CUFF.253988.1, which shares homology with human long noncoding RNA MALAT1. The findings of our study significantly increase the number of known lncRNAs in pigs.
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Ma, Zhonghua, Peng Peng, Jing Zhou, Bingqing Hui, Hao Ji, Juan Wang, and Keming Wang. "Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer." Cellular Physiology and Biochemistry 46, no. 6 (2018): 2197–214. http://dx.doi.org/10.1159/000489589.
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Background/Aims: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide. Current evidence has revealed the key roles of long non-coding RNAs (IncRNAs) in multiple cancers, including CRC. In this study we identified the lncRNA SH3PXD2A-AS1 as a novel molecule associated with CRC progression by analyzing the publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine the expression levels of SH3PXD2A-AS1 in CRC tissue samples and CRC cell lines. Cell viability examination, colony-formation experiments, ethynyl deoxyuridine (Edu) assays and flow cytometry were performed to investigate the roles of SH3PXD2A-AS1 in CRC proliferation, cell cycle regulation, and apoptosis. Transwell assays were used to explore the effects of SH3PXD2A-AS1 on CRC cells migration and invasion. A nude mice model was used to assess the effects of SH3PXD2A-AS1 on tumorigenesis in vivo. Subcellular fractionation, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays were conducted to detect the molecular mechanisms of SH3PXD2A-ASl-mediated gene expression. Rescue assays were used to determine whether P57 and Kruppel-like factor 2 (KLF2) were involved in SH3PXD2A-ASl-dependent CRC proliferation. Results: We firstly found that SH3PXD2A-AS1 was significantly upregulated in CRC tissues and cell lines, and overexpression of SH3PXD2A-AS1 was correlated with tumor size, TNM stage, and lymph node metastasis in patients with CRC. Furthermore, SH3PXD2A-AS1 knockdown inhibited CRC cells proliferation, migration and invasion in vitro, and suppressed tumorigenesis in vivo. Mechanistic studies indicated that SH3PXD2A-AS1 could epiqenetically repress P57 and KLF2 expression through interaction with EZH2. Rescue experiments suggested that SH3PXD2A-ASl-mediated oncogenesis was impaired by overexpression of P57 or KLF2. Interestingly, the expression of SH3PXD2A-AS1 was inversely correlated with the expression of P57 and KLF2 in CRC tissue samples. Conclusion: Our research presents the first evidence that SH3PXD2A-AS1 acts as an oncogene in CRC, and may be a promising diagnostic or therapeutic target in patients with CRC.
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Nuzziello, Nicoletta, and Maria Liguori. "The MicroRNA Centrism in the Orchestration of Neuroinflammation in Neurodegenerative Diseases." Cells 8, no. 10 (October 2, 2019): 1193. http://dx.doi.org/10.3390/cells8101193.
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MicroRNAs (miRNAs) are small non-coding RNAs with a unique ability to regulate the transcriptomic profile by binding to complementary regulatory RNA sequences. The ability of miRNAs to enhance (proinflammatory miRNAs) or restrict (anti-inflammatory miRNAs) inflammatory signalling within the central nervous system is an area of ongoing research, particularly in the context of disorders that feature neuroinflammation, including neurodegenerative diseases (NDDs). Furthermore, the discovery of competing endogenous RNAs (ceRNAs) has led to an increase in the complexity of miRNA-mediated gene regulation, with a paradigm shift from a unidirectional to a bidirectional regulation, where miRNA acts as both a regulator and is regulated by ceRNAs. Increasing evidence has revealed that ceRNAs, including long non-coding RNAs, circular RNAs, and pseudogenes, can act as miRNA sponges to regulate neuroinflammation in NDDs within complex cross-talk regulatory machinery, which is referred to as ceRNA network (ceRNET). In this review, we discuss the role of miRNAs in neuroinflammatory regulation and the manner in which cellular and vesicular ceRNETs could influence neuroinflammatory dynamics in complex multifactorial diseases, such as NDDs.
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Hong, Hyosun, Han-Ha Chai, Kyoungwoo Nam, Dajeong Lim, Kyung-Tai Lee, Yoon Do, Chang-Yeon Cho, and Jin-Wu Nam. "Non-Coding Transcriptome Maps across Twenty Tissues of the Korean Black Chicken, Yeonsan Ogye." International Journal of Molecular Sciences 19, no. 8 (August 10, 2018): 2359. http://dx.doi.org/10.3390/ijms19082359.
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Yeonsan Ogye is a rare Korean domestic chicken breed whose entire body, including feathers and skin, has a unique black coloring. Although some protein-coding genes related to this unique feature have been examined, non-coding elements have not been widely investigated. Thus, we evaluated coding and non-coding transcriptome expression and identified long non-coding RNAs functionally linked to protein-coding genes in Ogye. High-throughput RNA sequencing and DNA methylation sequencing were performed to profile the expression of 14,264 Ogye protein-coding and 6900 long non-coding RNA (lncRNA) genes and detect DNA methylation in 20 different tissues of an individual Ogye. Approximately 75% of Ogye lncRNAs and 45% of protein-coding genes showed tissue-specific expression. For some genes, tissue-specific expression levels were inversely correlated with DNA methylation levels in their promoters. Approximately 39% of tissue-specific lncRNAs displayed functional associations with proximal or distal protein-coding genes. Heat shock transcription factor 2-associated lncRNAs appeared to be functionally linked to protein-coding genes specifically expressed in black skin tissues, more syntenically conserved in mammals, and differentially expressed in black relative to in white tissues. Pending experimental validation, our findings increase the understanding of how the non-coding genome regulates unique phenotypes and can be used for future genomic breeding of chickens.
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Medina, José María, Muhammad Nadeem Abbas, Chaima Bensaoud, Michael Hackenberg, and Michail Kotsyfakis. "Bioinformatic Analysis of Ixodes ricinus Long Non-Coding RNAs Predicts Their Binding Ability of Host miRNAs." International Journal of Molecular Sciences 23, no. 17 (August 28, 2022): 9761. http://dx.doi.org/10.3390/ijms23179761.
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Ixodes ricinus ticks are distributed across Europe and are a vector of tick-borne diseases. Although I. ricinus transcriptome studies have focused exclusively on protein coding genes, the last decade witnessed a strong increase in long non-coding RNA (lncRNA) research and characterization. Here, we report for the first time an exhaustive analysis of these non-coding molecules in I. ricinus based on 131 RNA-seq datasets from three different BioProjects. Using this data, we obtained a consensus set of lncRNAs and showed that lncRNA expression is stable among different studies. While the length distribution of lncRNAs from the individual data sets is biased toward short length values, implying the existence of technical artefacts, the consensus lncRNAs show a more homogeneous distribution emphasizing the importance to incorporate data from different sources to generate a solid reference set of lncRNAs. KEGG enrichment analysis of host miRNAs putatively targeting lncRNAs upregulated upon feeding showed that these miRNAs are involved in several relevant functions for the tick-host interaction. The possibility that at least some tick lncRNAs act as host miRNA sponges was further explored by identifying lncRNAs with many target regions for a given host miRNA or sets of host miRNAs that consistently target lncRNAs together. Overall, our findings suggest that lncRNAs that may act as sponges have diverse biological roles related to the tick–host interaction in different tissues.
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Smalheiser, Neil R. "The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1652 (September 26, 2014): 20130504. http://dx.doi.org/10.1098/rstb.2013.0504.
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If mRNAs were the only RNAs made by a neuron, there would be a simple mapping of mRNAs to proteins. However, microRNAs and other non-coding RNAs (ncRNAs; endo-siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related transcripts, etc.) regulate mRNAs via effects on protein translation as well as transcriptional and epigenetic mechanisms. Not only are genes ON or OFF, but their ability to be translated can be turned ON or OFF at the level of synapses, supporting an enormous increase in information capacity. Here, I review evidence that ncRNAs are expressed pervasively within dendrites in mammalian brain; that some are activity-dependent and highly enriched near synapses; and that synaptic ncRNAs participate in plasticity responses including learning and memory. Ultimately, ncRNAs can be viewed as the post-it notes of the neuron. They have no literal meaning of their own, but derive their functions from where (and to what) they are stuck. This may explain, in part, why ncRNAs differ so dramatically from protein-coding genes, both in terms of the usual indicators of functionality and in terms of evolutionary constraints. ncRNAs do not appear to be direct mediators of synaptic transmission in the manner of neurotransmitters or receptors, yet they orchestrate synaptic plasticity—and may drive species-specific changes in cognition.
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Ghafari, Ayat B. Al-,., Halima A. Siddiqui, Hani M. Choudhry, Huda A. Al Doghaither, Huda F. Alshaibi, Hadeil M. Alsufiani, and Sawsan A. Rahimulddin. "Contribution of Long Non-Coding Rnas (Ccat1, Malat1, and Pandar) in the Pathogenesis of Colorectal Cancer." Pakistan Journal of Medical and Health Sciences 16, no. 2 (February 26, 2022): 512–17. http://dx.doi.org/10.53350/pjmhs22162512.
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Objectives: To assess the relationship between the expression of long non-coding RNAs (lncRNAs), CCAT1, MALAT1, and PANDAR, in CRC patients with varying physical, environmental, and pathophysiological factors. Material and Methods: A case-control study was conducted at King Abdulaziz University (Jeddah, Saudi Arabia). Whole blood was collected from 63 CRC patients and 40 healthy subjects in the period from January to August 2016. Anthropometric measurements were taken and the total RNA was isolated and the expression of lncRNA was determined by real-time polymerase chain reaction. Various software programs, including REST2009 and GraphPad Prism version 7, were used to analyze the different statistical correlations. Results: MALAT1 was significantly highly expressed in CRC female patients, whereas CCAT1 and PANDAR were significantly up-regulated in male CRC patients, as compared with controls. Moreover, in obese CRC patients, CCAT1, MALAT1, and PANDAR expressions were significantly up-regulated, while in overweight CRC patients, only MALAT1 was significantly more highly expressed, compared to controls. There was a slight increase in PANDAR expression in high-grade CRC patients, compared to low-grade patients. Finally, CCAT1 was significantly up-regulated in high fish intake CRC patients and was significantly correlated with smoking status. Conclusion: LncRNAs may contribute to CRC pathogenesis by affecting several physical and environmental factors. Keywords: Colorectal cancer, LncRNA CCAT1, LncRNA MALAT1, LncRNA PANDAR
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Zhang, Hanwen, Longping Yao, Zijian Zheng, Sumeyye Koc, and Guohui Lu. "The Role of Non-Coding RNAs in the Pathogenesis of Parkinson’s Disease: Recent Advancement." Pharmaceuticals 15, no. 7 (June 30, 2022): 811. http://dx.doi.org/10.3390/ph15070811.
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Parkinson’s disease (PD) is a prevalent neurodegenerative aging disorder that manifests as motor and non-motor symptoms, and its etiopathogenesis is influenced by non-coding RNAs (ncRNAs). Signal pathway and gene sequence studies have proposed that alteration of ncRNAs is relevant to the occurrence and development of PD. Furthermore, many studies on brain tissues and body fluids from patients with PD indicate that variations in ncRNAs and their target genes could trigger or exacerbate neurodegenerative pathogenesis and serve as potential non-invasive biomarkers of PD. Numerous ncRNAs have been considered regulators of apoptosis, α-syn misfolding and aggregation, mitochondrial dysfunction, autophagy, and neuroinflammation in PD etiology, and evidence is mounting for the determination of the role of competing endogenous RNA (ceRNA) mechanisms in disease development. In this review, we discuss the current knowledge regarding the regulation and function of ncRNAs as well as ceRNA networks in PD pathogenesis, focusing on microRNAs, long ncRNAs, and circular RNAs to increase the understanding of the disease and propose potential target identification and treatment in the early stages of PD.
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Briones Martin del Campo, Marcela C., Alex Lee, Max Horlbeck, Truc Dinh, Marta Roman-Moreno, Leanne Sayles, Bokyung Seong, Kimberly Stegmaier, Luke Gilbert, and E. Alejandro Sweet-Cordero. "Abstract B021: Long non-coding RNAs that are required for robust cell growth in ewing Sarcoma." Clinical Cancer Research 28, no. 18_Supplement (September 15, 2022): B021. http://dx.doi.org/10.1158/1557-3265.sarcomas22-b021.
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Abstract While long non-coding RNAs (lncRNAs) are upregulated in many cancers, their role in pediatric cancers is unclear. Among pediatric cancers, Ewing sarcoma is unique in that these tumors show upregulation of a large, specific number of lncRNAs. To perform an unbiased screen of lncRNA function in Ewing sarcoma, we used a pooled CRISPRi screen to identify lncRNAs that modify cell growth. We included in the pooled library lncRNAs either highly expressed in Ewing Sarcoma or directly regulated by the driving oncogene in Ewing Sarcoma, EWS-FLI. We identified 49 lncRNAs that when inhibited by CRISPRi led to decreased growth of Ewing cell lines. Among those that scored most significantly were the small nucleolar host genes SNHG1, SNHG12, and SNHG30. To validate the screening results, we individually cloned the two most depleted sgRNAs targeting for each of these three lncRNAs into a lentiviral vector. We expressed these sgRNAs in three different dCas9-KRAB+ Ewing cell lines and used internally controlled growth assays to test whether the observed phenotypes from the screens were reproducible. We confirmed that for all three lncRNAs hits significantly affected Ewing’s growth, and their depletion leads to an increase in apoptosis. To determine how lncRNAs influence the ability of Ewing sarcoma cells to growth and survive in vivo, we performed a subcutaneous xenograft CRISPRi screen using the same pooled library used in vitro. The lncRNAs with the strongest pro-growth phenotype after knock-down were PVT1 and the uncharacterized LINC02688. Ongoing studies are directed at determining the Ewing-specific role of these lncRNAs. Overall, our studies demonstrate the value of studying lncRNA functions in vitro and in vivo, provides a valuable resource of new lncRNAs targets to further research and establishes a framework for systematic discovery of functional lncRNAs in Ewing cells. Citation Format: Marcela C. Briones Martin del Campo, Alex Lee, Max Horlbeck, Truc Dinh, Marta Roman-Moreno, Leanne Sayles, Bokyung Seong, Kimberly Stegmaier, Luke Gilbert, E. Alejandro Sweet-Cordero. Long non-coding RNAs that are required for robust cell growth in ewing Sarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B021.
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Ogoyama, Manabu, Hironori Takahashi, Hirotada Suzuki, Akihide Ohkuchi, Hiroyuki Fujiwara, and Toshihiro Takizawa. "Non-Coding RNAs and Prediction of Preeclampsia in the First Trimester of Pregnancy." Cells 11, no. 15 (August 5, 2022): 2428. http://dx.doi.org/10.3390/cells11152428.
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Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The only fundamental treatment for PE is the termination of pregnancy. Therefore, not only severe maternal complications but also perinatal complications due to immaturity of the infant associated with early delivery are serious issues. The treatment and prevention of preterm onset preeclampsia (POPE) are challenging. In 2017, the ASPRE trial showed that a low oral dose of aspirin administered to POPE high-risk women in early pregnancy reduced POPE by 62%. A prediction algorithm at 11–13 weeks of gestation identifies POPE with 75% sensitivity when the false positive rate is set at 10%. New biomarkers to increase the accuracy of the prediction model for POPE high-risk women in early pregnancy are needed. In this review, we focused on non-coding RNAs (ncRNAs) as potential biomarkers for the prediction of POPE. Highly expressed ncRNAs in the placenta in early pregnancy may play crucial roles in placentation. Furthermore, placenta-specific ncRNAs have been detected in maternal blood. In this review, we summarized ncRNAs that were highly expressed in the primary human placenta in early pregnancy. We also presented highly expressed ncRNAs in the placenta that were associated with or predictive of the development of PE in an expression analysis of maternal blood during the first trimester of pregnancy. These previous studies showed that the chromosome 19 microRNA (miRNA) -derived miRNAs (e.g., miR-517-5p, miR-518b, and miR-520h), the hypoxia-inducible miRNA (miR-210), and long non-coding RNA H19, were not only highly expressed in the early placenta but were also significantly up-regulated in the blood at early gestation in pregnant women who later developed PE. These maternal circulating ncRNAs in early pregnancy are expected to be possible biomarkers for POPE.
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Sharma, Uttam, Tushar Barwal, Varnali Acharya, Karuna Singh, Manjit Rana, Satyendra Singh, Hridayesh Prakash, Anupam Bishayee, and Aklank Jain. "Long Non-Coding RNAs as Strategic Molecules to Augment the Radiation Therapy in Esophageal Squamous Cell Carcinoma." International Journal of Molecular Sciences 21, no. 18 (September 16, 2020): 6787. http://dx.doi.org/10.3390/ijms21186787.
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Intrinsic resistance to ionizing radiation is the major impediment in the treatment and clinical management of esophageal squamous cell carcinoma (ESCC), leading to tumor relapse and poor prognosis. Although several biological and molecular mechanisms are responsible for resistance to radiotherapy in ESCC, the molecule(s) involved in predicting radiotherapy response and prognosis are still lacking, thus requiring a detailed understanding. Recent studies have demonstrated an imperative correlation amongst several long non-coding RNAs and their involvement in complex cellular networks like DNA damage and repair, cell cycle, apoptosis, proliferation, and epithelial-mesenchymal transition. Additionally, accumulating evidence has suggested abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy effects in tumor cells’ sensitivity. Thus, lncRNAs indeed represent unique molecules that can influence tumor cell susceptibility for various clinical interventions. On this note, herein, we have summarized the current status of lncRNAs in augmenting resistance/sensitivity in ESCC against radiotherapy. In addition, we have also discussed various strategies to increase the radiosensitivity in ESCC cells under clinical settings.
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Huang, Guangxin, Yan Kang, Zhiyu Huang, Zhiqi Zhang, Fangang Meng, Weishen Chen, Ming Fu, Weiming Liao, and Ziji Zhang. "Identification and Characterization of Long Non-Coding RNAs in Osteogenic Differentiation of Human Adipose-Derived Stem Cells." Cellular Physiology and Biochemistry 42, no. 3 (2017): 1037–50. http://dx.doi.org/10.1159/000478751.
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Background/Aims: Long noncoding RNAs (lncRNAs) play important roles in stem cell differentiation. However, their role in osteogenesis of human adipose-derived stem cells (ASCs), a promising cell source for bone regeneration, remains unknown. Here, we investigated the expression profile and potential roles of lncRNAs in osteogenic differentiation of human ASCs. Methods: Human ASCs were induced to differentiate into osteoblasts in vitro, and the expression profiles of lncRNAs and mRNAs in undifferentiated and osteogenic differentiated ASCs were obtained by microarray. Bioinformatics analyses including subgroup analysis, gene ontology analysis, pathway analysis and co-expression network analysis were performed. The function of lncRNA H19 was determined by in vitro knockdown and overexpression. Quantitative reverse transcription polymerase chain reaction was utilized to examine the expression of selected genes. Results: We identified 1,460 upregulated and 1,112 downregulated lncRNAs in osteogenic differentiated human ASCs as compared with those of undifferentiated cells (Fold change ≥ 2.0, P < 0.05). Among these, 94 antisense lncRNAs, 85 enhancer-like lncRNAs and 160 lincRNAs were further recognized. We used 12 lncRNAs and 157 mRNAs to comprise a coding-non-coding gene expression network. Additionally, silencing of H19 caused a significantly increase in expression of osteogenesis-related genes, including ALPL and RUNX2, while a decrease was observed after H19 overexpression. Conclusion: This study revealed for the first time the global expression profile of lncRNAs involved in osteogenic differentiation of human ASCs and provided a foundation for future investigations of lncRNA regulation of human ASC osteogenesis.
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Zucchelli, Silvia, Laura Patrucco, Francesca Persichetti, Stefano Gustincich, and Diego Cotella. "Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs." Computational and Structural Biotechnology Journal 14 (2016): 404–10. http://dx.doi.org/10.1016/j.csbj.2016.10.004.
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Tripathi, Manish, Chidi Zacheaus, Kyle Doxtater, Fatemeh Keramatnia, Cuilan Gao, Murali Yallapu, Meena Jaggi, and Subhash Chauhan. "Z Probe, An Efficient Tool for Characterizing Long Non-Coding RNA in FFPE Tissues." Non-Coding RNA 4, no. 3 (September 5, 2018): 20. http://dx.doi.org/10.3390/ncrna4030020.
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Formalin-fixed paraffin embedded (FFPE) tissues are a valuable resource for biomarker discovery in order to understand the etiology of different cancers and many other diseases. Proteins are the biomarkers of interest with respect to FFPE tissues as RNA degradation is the major challenge in these tissue samples. Recently, non-protein coding transcripts, long non-coding RNAs (lncRNAs), have gained significant attention due to their important biological actions and potential involvement in cancer. RNA sequencing (RNA-seq) or quantitative reverse transcription-polymerase chain reaction (qRT-PCR) are the only validated methods to evaluate and study lncRNA expression and neither of them provides visual representation as immunohistochemistry (IHC) provides for proteins. We have standardized and are reporting a sensitive Z probe based in situ hybridization method to visually identify and quantify lncRNA in FFPE tissues. This assay is highly sensitive and identifies transcripts visible within different cell types and tumors. We have detected a scarcely expressed tumor suppressor lncRNA NRON (non-coding repressor of nuclear factor of activated T-cells (NFAT)), a moderately expressed oncogenic lncRNA UCA1 (urothelial cancer associated 1), and a highly studied and expressed lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) in different cancers. High MALAT1 staining was found in colorectal, breast and pancreatic cancer. Additionally, we have observed an increase in MALAT1 expression in different stages of colorectal cancer.
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Słomka, Artur, Miroslaw Kornek, and William C. Cho. "Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review." Cells 11, no. 18 (September 17, 2022): 2913. http://dx.doi.org/10.3390/cells11182913.
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In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) in cancer. Thanks to advancements in molecular biology, it has been found that the fraction of EVs called exosomes or small EVs (sEVs) modulates the sensitivity of cancer cells to chemotherapeutic agents by delivering molecularly active non-coding RNAs (ncRNAs). An in-depth analysis shows that two main molecular mechanisms are involved in exosomal modified chemoresistance: (1) translational repression of anti-oncogenes by exosomal microRNAs (miRs) and (2) lack of translational repression of oncogenes by sponging of miRs through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). At the cellular level, these processes increase the proliferation and survival of cancer cells and improve their ability to metastasize and resist apoptosis. In addition, studies in animal models have shown enhancing tumor size under the influence of exosomal ncRNAs. Ultimately, exosomal ncRNAs are responsible for clinically significant chemotherapy failures in patients with different types of cancer. Preliminary data have also revealed that exosomal ncRNAs can overcome chemotherapeutic agent resistance, but the results are thoroughly fragmented. This review presents how exosomes modulate the response of cancer cells to chemotherapeutic agents. Understanding how exosomes interfere with chemoresistance may become a milestone in developing new therapeutic options, but more data are still required.
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Kumar, Baibhav, Animesh Kumar, Sarika Jaiswal, Mir Asif Iquebal, Ulavappa B. Angadi, Rukam S. Tomar, Anil Rai, and Dinesh Kumar. "Genome-Wide Identification of Long Non-Coding RNAs in Pearl Millet (Pennisetum glaucum (L.)) Genotype Subjected to Drought Stress." Agronomy 12, no. 8 (August 22, 2022): 1976. http://dx.doi.org/10.3390/agronomy12081976.
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Pearl millet (Pennisetum glaucum L.) is affected by drought stress, affecting crop productivity and survival. Long non-coding RNAs (lncRNAs) are reported to play a vital role in the response to drought stress. LncRNAs represent a major part of non-protein coding RNAs and are present prevalently. These are involved in various biological processes, which may functionally act as RNA rather than getting transcribed as protein. We targeted genome-wide identification of lncRNAs in pearl millet from root and leaf tissues subjected to drought stress. A total of 879 lncRNAs were identified, out of which 209 (leaf control, root control), 198 (leaf treated, root treated), 115 (leaf control, leaf treated) and 194 (root control, root treated) were differentially expressed. Two lncRNAs were found as potential target mimics of three miRNAs from the miRBase database. Gene ontology study revealed that drought-responsive lncRNAs are involved in biological processes like ‘metabolic process’ and ‘cellular process’, molecular functions like ‘binding’ and ‘catalytic activities’ and cellular components like ‘cell’, ‘cell part’ and ‘membrane part’. LncRNA-miRNA-mRNA network shows that it plays a vital role in the stress-responsive mechanism through their activities in hormone signal transduction, response to stress, response to auxin and transcription factor activity. Only four lncRNAs were found to get a match with the lncRNAs present in the plant lncRNA database CANTATAdb, which shows its poorly conserved nature among species. This information has been cataloged in the pearl millet drought-responsive long non-coding RNA database (PMDlncRDB). The discovered lncRNAs can be used in the improvement of important traits, as well as CISPR-Cas technology, in the editing of ncRNAs in plants for trait improvement. Such a study will increase our understanding of the expression behavior of lncRNAs, as well as its underlying mechanisms under drought stress in pearl millet.
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Салеева, Д. В., В. Ф. Михайлов, Л. В. Шуленина, В. В. Виноградов, А. А. Бахтин, К. В. Акопян, М. В. Незнанова, and Г. Д. Засухина. "Activities of regulatory RNAs that affect development of tumor cells in patients with laryngeal cancer." ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia», no. 4() (November 21, 2018): 67–74. http://dx.doi.org/10.25557/0031-2991.2018.04.67-74.
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Цель. Определение прогностической значимости и роли экспрессии некодирующих РНК (длинные РНК и микроРНК), и белка кодирующих генов в патогенезе рака гортани. Методика. Исследован биопсийный материал и периферическая кровь 35 пациентов с диагнозом плоскоклеточный рак гортани (ПРГ) с классификацией от T1N0M0 до T4N1M0. Контролем служили образцы близлежащей гистологически неизмененной ткани гортани тех же больных. Для оценки экспрессии генов исследовали кровь 27 здоровых доноров. Содержание мРНК генов ( р53, CCND1, ORAOV1, hPTEN ), длинных некодирующих РНК (днРНК): NEAT1, MALAT1, ROR , а также зрелых микроРНК (miR-21, miR-27a, miR-34a, miR-101, miR-124, miR-125b, miR-181а) в опухолевой ткани и крови определяли методом ПЦР в реальном времени (ПЦР-РВ). Результаты. Выявлено увеличение содержания мРНК генов CCND1, hPTEN , днРНК NEAT1, MALAT1 и miR-21, miR-27a в крови у пациентов с ПРГ. Установлено, что уровень мРНК генов CCND1, ORAOV1 был значимо выше при исследовании биоптатов у больных 3-й - 4-й стадии, чем у больных 1-й - 2-й стадии заболевания. Такая же закономерность выявлена для днРНК NEAT1, MALAT1 и для miR-101. Экспрессия miR-27a и miR-124 на более поздних стадиях болезни была ниже, чем у пациентов 1-2 стадии. Заключение. Выявлена возможность использования исследованных днРНК, микроРНК и мРНК белоккодирующих генов для индивидуального прогноза заболевания при создании панели биомаркеров. Aim. To study the role of non-coding RNA (long RNAs and microRNAs) expression and protein-coding genes in the pathogenesis of laryngeal cancer to determine their prognostic significance for oncotransformation. Methods. The expression of long non-coding RNAs, microRNAs and protein-coding genes was examined in biopsy samples (fresh frozen tissue) and peripheral blood samples from 35 patients with laryngeal squamous cell cancer (LSCC) at T1N0M0 - T4N1M0 stages. Samples of surrounding, histologically unchanged tissues collected from the same patients were used as control. Gene expression was evaluated in blood samples from 27 healthy donors. Contents of gene mRNAs ( p53, CCND1, ORAOV1, hPTEN ), long non-coding RNAs (IncRNA) ( NEAT1, MALAT1, ROR ), and mature miRNAs (miR-21, miR-27a, miR-34a, miR-101, miR-124, miR -125b, miR-181a) were measured in tissue and blood using real-time PCR. Results. Contents of CCND1 and hPTEN gene mRNAs, lncRNAs ( NEAT1, MALAT1), miR-21, and miR-27a were increased in blood of patients with LSCC. Levels of CCND1 and ORAOV1 gene mRNAs were significantly higher in biopsy samples from stage 3-4 patients compared to stage 1-2 patients. A similar expression pattern was observed for lncRNAs NEAT1 and MALAT1 and miR-101. On the other hand, expression of miR-27a and miR-124 was lower at later stages than at stages 1-2. Conclusion. The studied lncRNAs, microRNAs and protein-coding genes can be used in development of a biomarker panel for individual prognosis of the disease.
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Militello, Giuseppe, Mohammed Rabiul Hosen, Yuliya Ponomareva, Pascal Gellert, Tyler Weirick, David John, Sajedah Mahmoud Hindi, et al. "A novel long non-coding RNA Myolinc regulates myogenesis through TDP-43 and Filip1." Journal of Molecular Cell Biology 10, no. 2 (April 1, 2018): 102–17. http://dx.doi.org/10.1093/jmcb/mjy025.
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Abstract Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of lncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identified a novel muscle-enriched lncRNA called ‘Myolinc (AK142388)’, which we functionally characterized in the C2C12 myoblast cell line. Myolinc is predominately localized in the nucleus, and its levels increase upon induction of the differentiation. Knockdown of Myolinc impairs the expression of myogenic regulatory factors and formation of multi-nucleated myotubes in cultured myoblasts. Myolinc also regulates the expression of Filip1 in a cis-manner. Similar to Myolinc, knockdown of Filip1 inhibits myogenic differentiation. Furthermore, Myolinc binds to TAR DNA-binding protein 43 (TDP-43), a DNA/RNA-binding protein that regulates the expression of muscle genes (e.g. Acta1 and MyoD). Knockdown of TDP-43 inhibits myogenic differentiation. We also show that Myolinc−TDP-43 interaction is essential for the binding of TDP-43 to the promoter regions of muscle marker genes. Finally, we show that silencing of Myolinc inhibits skeletal muscle regeneration in adult mice. Altogether, our study identifies a novel lncRNA that controls key regulatory networks of myogenesis.
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Cardamone, Giulia, Elvezia M. Paraboschi, Giulia Soldà, Claudia Cantoni, Domenico Supino, Laura Piccio, Stefano Duga, and Rosanna Asselta. "Not only cancer: the long non-coding RNA MALAT1 affects the repertoire of alternatively spliced transcripts and circular RNAs in multiple sclerosis." Human Molecular Genetics 28, no. 9 (December 19, 2018): 1414–28. http://dx.doi.org/10.1093/hmg/ddy438.
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AbstractLong non-coding RNAs (lncRNAs) are post-transcriptional and epigenetic regulators, whose implication in neurodegenerative and autoimmune diseases remains poorly understood. We analyzed publicly available microarray data sets to identify dysregulated lncRNAs in multiple sclerosis (MS), a neuroinflammatory autoimmune disease. We found a consistent upregulation in MS of the lncRNA MALAT1 (2.7-fold increase; meta-analysis, P = 1.3 × 10−8; 190 cases, 182 controls), known to regulate alternative splicing (AS). We confirmed MALAT1 upregulation in two independent MS cohorts (1.5-fold increase; P < 0.01; 59 cases, 50 controls). We hence performed MALAT1 overexpression/knockdown in cell lines, demonstrating that its modulation impacts on endogenous expression of splicing factors (HNRNPF and HNRNPH1) and on AS of MS-associated genes (IL7R and SP140). Minigene-based splicing assays upon MALAT1 modulation recapitulated IL7R and SP140 isoform unbalances observed in patients. RNA-sequencing of MALAT1-knockdown Jurkat cells further highlighted MALAT1 role in splicing (approximately 1100 significantly-modulated AS events) and revealed its contribution to backsplicing (approximately 50 differentially expressed circular RNAs). Our study proposes a possible novel role for MALAT1 dysregulation and the consequent AS alteration in MS pathogenesis, based on anomalous splicing/backsplicing profiles of MS-relevant genes.
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Rudzinska, Magdalena, Karolina H. Czarnecka-Chrebelska, Ekaterina B. Kuznetsova, Sofya V. Maryanchik, Alessandro Parodi, Dmitry O. Korolev, Nataliya Potoldykova, et al. "Long Non-Coding PROX1-AS1 Expression Correlates with Renal Cell Carcinoma Metastasis and Aggressiveness." Non-Coding RNA 7, no. 2 (April 10, 2021): 25. http://dx.doi.org/10.3390/ncrna7020025.
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Long non-coding RNAs (lncRNAs) can be specifically expressed in different tissues and cancers. By controlling the gene expression at the transcriptional and translational levels, lncRNAs have been reported to be involved in tumor growth and metastasis. Recent data demonstrated that multiple lncRNAs have a crucial role in renal cell carcinoma (RCC) progression—the most common malignant urogenital tumor. In the present study, we found a trend towards increased PROX1 antisense RNA 1 (PROX1-AS1) expression in RCC specimens compared to non-tumoral margins. Next, we found a positive correlation between PROX1-AS1 expression and the occurrence of distant and lymph node metastasis, higher tumor stage (pT1 vs. pT2 vs. pT3–T4) and high-grade (G1/G2 vs. G3/G4) clear RCC. Furthermore, global demethylation in RCC-derived cell lines (769-P and A498) and human embryonic kidney 293 (HEK293) cells induced a significant increase of PROX1-AS1 expression level, with the most remarkable change in HEK293 cells. In line with this evidence, bisulfite sequencing analysis confirmed the specific demethylation of bioinformatically selected CpG islands on the PROX1-AS1 promoter sequence in the HEK293 cell line but not in the tumor cells. Additionally, the human specimen analysis showed the hemimethylated state of CG dinucleotides in non-tumor kidney tissues, whereas the tumor samples presented the complete, partial, or no demethylation of CpG-islands. In conclusion, our study indicated that PROX1-AS1 could be associated with RCC progression, and further investigations may define its role as a new diagnostic marker and therapeutic target.
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Cardoso, Ana M., Catarina M. Morais, Olinda Rebelo, Hermínio Tão, Marcos Barbosa, Maria C. Pedroso de Lima, and Amália S. Jurado. "Downregulation of long non-protein coding RNA MVIH impairs glioblastoma cell proliferation and invasion through an miR-302a-dependent mechanism." Human Molecular Genetics 30, no. 1 (January 1, 2021): 46–64. http://dx.doi.org/10.1093/hmg/ddab009.
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Abstract Glioblastoma (GB) is the most frequent and malignant type of brain tumor, for which no effective therapy exists. The high proliferative and invasive nature of GB, as well as its acquired resistance to chemotherapy, makes this type of cancer extremely lethal shortly after diagnosis. Long non-protein coding RNAs (lncRNA) are a class of regulatory RNAs whose levels can be dysregulated in the context of diseases, unbalancing several physiological processes. The lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA-MVIH), overexpressed in several cancers, was described to co-precipitate with phosphoglycerate kinase 1 (PGK1), preventing secretion of this enzyme to the extracellular environment and promoting cell migration and invasion. We hypothesized that, by silencing the expression of lncRNA-MVIH, the secretion of PGK1 would increase, reducing GB cell migration and invasion capabilities. We observed that lncRNA-MVIH silencing in human GB cells significantly decreased glycolysis, cell growth, migration, and invasion and sensitized GB cells to cediranib. However, no increase in extracellular PGK1 was observed as a consequence of lncRNA-MVIH silencing, and therefore, we investigated the possibility of a mechanism of miRNA sponge of lncRNA-MVIH being in place. We found that the levels of miR-302a loaded onto RISC increased in GB cells after lncRNA-MVIH silencing, with the consequent downregulation of several miR-302a molecular targets. Our findings suggest a new mechanism of action of lncRNA-MVIH as a sponge of miR-302a. We suggest that lncRNA-MVIH knockdown may be a promising strategy to address GB invasiveness and chemoresistance, holding potential towards its future application in a clinical context.
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Donati, Simone, Cinzia Aurilia, Gaia Palmini, Irene Falsetti, Teresa Iantomasi, and Maria Luisa Brandi. "Autophagy-Related ncRNAs in Pancreatic Cancer." Pharmaceuticals 15, no. 12 (December 13, 2022): 1547. http://dx.doi.org/10.3390/ph15121547.
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Pancreatic cancer (PC) is a malignancy accounting for only 3% of total cancers, but with a low 5-year relative survival rate. Approximately 80% of PC patients are diagnosed at a late stage when the disease has already spread from the primary site. Despite advances in PC treatment, there is an urgently needed for the identification of novel therapeutic strategies for PC, particularly for patients who cannot undergo classical surgery. Autophagy is an evolutionarily conserved process used by cells to adapt to metabolic stress via the degrading or recycling of damaged or unnecessary organelles and cellular components. This process is elevated in PC and, thus, it contributes to the onset, progression, and cancer cell resistance to chemotherapy in pancreatic tumors. Autophagy inhibition has been shown to lead to cancer regression and to increase the sensitivity of pancreatic cells to radiation and chemotherapy. Emerging studies have focused on the roles of non-coding RNAs (ncRNAs), such as miRNAs, long non-coding RNAs, and circular RNAs, in PC development and progression. Furthermore, ncRNAs have been reported as crucial regulators of many biological processes, including autophagy, suggesting that ncRNA-based autophagy targeting methods could be promising novel molecular approaches for specifically reducing autophagic flux, thus improving the management of PC patients. In this review, we briefly summarize the existing studies regarding the role and the regulatory mechanisms of autophagy-related ncRNAs in the context of this cancer.
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Lee, Adam M., Asmaa Ferdjallah, Elise Moore, Daniel C. Kim, Aritro Nath, Emily Greengard, and R. Stephanie Huang. "Long Non-Coding RNA ANRIL as a Potential Biomarker of Chemosensitivity and Clinical Outcomes in Osteosarcoma." International Journal of Molecular Sciences 22, no. 20 (October 16, 2021): 11168. http://dx.doi.org/10.3390/ijms222011168.
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Osteosarcoma has a poor prognosis due to chemo-resistance and/or metastases. Increasing evidence shows that long non-coding RNAs (lncRNAs) can play an important role in drug sensitivity and cancer metastasis. Using osteosarcoma cell lines, we identified a positive correlation between the expression of a lncRNA and ANRIL, and resistance to two of the three standard-of-care agents for treating osteosarcoma—cisplatin and doxorubicin. To confirm the potential role of ANRIL in chemosensitivity, we independently inhibited and over-expressed ANRIL in osteosarcoma cell lines followed by treatment with either cisplatin or doxorubicin. Knocking-down ANRIL in SAOS2 resulted in a significant increase in cellular sensitivity to both cisplatin and doxorubicin, while the over-expression of ANRIL in both HOS and U2OS cells led to an increased resistance to both agents. To investigate the clinical significance of ANRIL in osteosarcoma, we assessed ANRIL expression in relation to clinical phenotypes using the osteosarcoma data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset. Higher ANRIL expression was significantly associated with increased rates of metastases at diagnosis and death and was a significant predictor of reduced overall survival rate. Collectively, our results suggest that the lncRNA ANRIL can be a chemosensitivity and prognosis biomarker in osteosarcoma. Furthermore, reducing ANRIL expression may be a therapeutic strategy to overcome current standard-of-care treatment resistance.
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Alfaifi, Mohammed, Mirza Masroor Ali Beg, Mohammed Yahya Alshahrani, Irfan Ahmad, Ali Gaithan Alkhathami, Prakash C. Joshi, Osama M. Alshehri, Abdulrahman Manaa Alamri, and Amit Kumar Verma. "Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus." BMJ Open Diabetes Research & Care 9, no. 1 (January 2021): e001821. http://dx.doi.org/10.1136/bmjdrc-2020-001821.
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BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial disorder that leads to alterations in gene regulation. Long non-coding RNAs (lncRNAs) have become a major research topic as they are involved in metabolic disorders.MethodsThis study included a total of 400 study subjects; 200 were subjects with T2DM and 200 were healthy subjects. Extracted RNA was used to synthesize cDNA by quantitative real time. Serum analysis was carried out to determine differences in biochemical parameters. Recorded data were used to evaluate associations with expression of lncRNAs NF-kappaB interacting lncRNA (NKILA), nuclear enriched abundant transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and myocardial infarction-associated transcript (MIAT) in T2DM cases.ResultsCompared with healthy controls, patients with T2DM showed an overall increase in expression of lncRNAs NKILA, NEAT, MALAT1, and MIAT by 3.94-fold, 5.28-fold, 4.46-fold, and 6.35-fold, respectively. Among patients with T2DM, higher expression of lncRNA NKILA was associated with hypertension (p=0.001), smoking (p<0.0001), and alcoholism (p<0.0001). Altered NEAT1 expression was significantly associated with weight loss (p=0.04), fatigue (p=0.01), slow wound healing (p=0.002), blurred vision (p=0.008), loss of appetite (p=0.007), smoking (p<0.0001), and alcoholism (p<0.0001). Higher expression of lncRNA MALAT1 was significantly linked with weight loss (p=0.003), blurred vision (p=0.01), smoking (p<0.0001), and alcoholism (p<0.0001). Expression of lncRNA MIAT was associated with only blurred vision (p<0.0001), smoking (p<0.0001), and alcoholism (p<0.0001). Positive correlations of lncRNA NKILA with lncRNAs NEAT1 (r=0.42, p<0.0001), MALAT (r=0.36, p<0.0001) and MIAT (r=0.42, p<0.0001) were observed among patients with T2DM. Significant positive correlations of lncRNA NEAT with lncRNAs MALAT and MIAT were observed among patients with T2DM. A positive correlation between lncRNAs MALAT and MIAT was also observed among patients with T2DM.ConclusionIncreased circulating NKILA, NEAT1, MALAT, and MIAT expression in patients with T2DM, which is linked with poor patient outcomes and significantly linked with alcoholism and smoking, may influence the degree and severity of disease among patients with T2DM. These lncRNAs may contribute to the progression of T2DM disease or other related diabetes-related complications.
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Sui, Jidong, Xuejun Yang, Wenjing Qi, Kun Guo, Zhenming Gao, Liming Wang, and Deguang Sun. "Long Non-Coding RNA Linc-USP16 Functions As a Tumour Suppressor in Hepatocellular Carcinoma by Regulating PTEN Expression." Cellular Physiology and Biochemistry 44, no. 3 (2017): 1188–98. http://dx.doi.org/10.1159/000485449.
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Background/Aims: Recent evidence has indicated the crucial regulatory roles of long non-coding RNAs (lncRNAs) in tumour biology. In hepatocellular carcinoma (HCC), aberrant expression of lncRNAs plays an essential role in HCC tumourigenesis. However, the potential roles and regulatory mechanisms of the novel human lncRNA, Linc-USP16, in HCC are unclear. Methods: To investigate the function of Linc-USP16 in HCC, we first analysed the expression levels of Linc-USP16 in HCC patient tissues and cell lines via q-RT-PCR and established overexpressed or knockdown HCC cell lines. Results: Here, we found that Linc-USP16 expression was significantly down-regulated in HCC patient tissues and cell lines. Further functional experiments suggested that Linc-USP16 could directly increase PTEN expression by acting as a competing endogenous RNA (ceRNA) for miR-21 and miR-590-5p. These interactions led to repression of AKT pathway and inhibition of HCC cell proliferation and migration. Conclusion: Thus, our data showed that Linc-USP16, as a tumour suppressor, plays an important role in HCC pathogenesis and provides a new therapeutic strategy for HCC treatment.
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Milenkovic, Dragan, Jiye Kang, Ziwei Wang, Eleonora Cremonini, David Vauzour, and Patricia Oteiza. "Epicatechin Mitigates Anxiety-Related Behavior in a Mouse Model of Obesity by Modulating Gut Microbiome Composition and Global Gene Expression Profile in the Hippocampus." Current Developments in Nutrition 6, Supplement_1 (June 2022): 316. http://dx.doi.org/10.1093/cdn/nzac053.057.
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Abstract Objectives Epicatechin (EC) is a flavan-3-ol abundant in cocoa, apples, and tea, and can prevent vascular dysfunction and development of diseases, such as cardiovascular or neurodegenerative diseases. We have recently shown that EC can prevent lipid-induced brain endothelial cell dysfunction by modulating the expression of protein-coding and non-coding genes (miRNAs, long non-coding RNAs). The aim of our study is to investigate the capacity of EC to mitigate the adverse effects of high-fat diet (HFD) on cognitive function, the gut microbiota dysbiosis, metabolic and inflammatory markers as well as to decipher the molecular mechanisms of EC action. Methods Healthy eight-weeks old male mice were fed for 24 weeks either: A) a control diet containing 10% total calories from fat; B) a HFD containing 45% total calories from fat; or c) a HFD supplemented with EC (20 mg/kg BW). Plasma metabolic parameters, cognitive tests (open field test, novel object recognition test, Morris water maze), gut microbiota profile (16S sequencing), and genomic modifications (Affymetrix arrays) in the hippocampus followed by in-depth bioinformatic analyses were performed. Results EC supplementation resulted in amelioration of HFD-induced increase in plasma glucose and insulin, mitigated anxiety-related behaviors and modulated affected the microbiota composition by affecting abundance of 139 taxa. Transcriptomic analysis demonstrated that EC induced significant changes in the hippocampal gene expression of mice fed with the HFD. We observed changes in expression of 1001 genes corresponding to protein-coding genes, 241 miRNAs, and 167 long non-coding RNAs. The PCA and heatmap analysis revealed opposite expression of genes obtained following EC supplementation when compared to the gene expression profile obtained after consumption of the HFD. Functionality analysis revealed that the differentially expressed gene regulate processes involved in neurofunction, inflammation, cell-cell adhesion, and cell signaling. Conclusions In summary, EC supplementation mitigated anxiety-related behavior in a model of diet-induced obesity in mice, which can be in part mediated through the modulation of gut microbiota and by reversing HFD-induced complex genomic modification in the hippocampus. Funding Sources NIH grants R01DK090492 and R01DK095359. France-Barkley foundation.
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Congrains, Ada, João Agostinho Machado-Neto, Flávia Adolfo Corrocher, Renata Giardini Rosa, Fernanda Soares Niemann, and Sara Teresinha Olalla Saad. "Antisense Long Non-Coding RNA in the LEF1 Locus Regulates Sense LEF1 Expression in Leukemic Cell Line KG1." Blood 126, no. 23 (December 3, 2015): 3586. http://dx.doi.org/10.1182/blood.v126.23.3586.3586.
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Abstract Aberrant regulation of the WNT signaling pathway is a signature in numerous human cancers. Lymphoid enhancer-binding factor-1 (LEF1) is an important transcription factor downstream of this pathway. LEF1 over-expression induces AML in mice and plays a critical role in hematopoietic cell differentiation (Petropoulos et al JME 2008). Reduction of LEF1 expression through the progression of myelodysplastic syndrome has been reported and further supports the relevance of this gene in the disease pathogenesis (Pellagatti et al Br J Haematol. 2009). Our previous work using microarray technology revealed a decreased expression of a long non-coding RNA antisense to LEF1 (LEF1-AS) in MDS patients (Baratti et al BMC Medical Genomics 2010). Mounting evidence suggests that long non-coding transcripts play important roles in the epigenetic regulation of coding genes. In this context it is not surprising that long non-coding RNAs are emerging as key players in disease development and progression. Non-coding expression overlapping coding genes is very common and several examples of local regulation have been described in the literature. Here we investigate for the first time the role of LEF1 antisense long non-coding in hematopoiesis and demonstrated its contribution in the regulation of the LEF1 locus in a leukemic cell line. To explore a possible role of LEF1-AS in differentiation, we evaluated the expression pattern of LEF1-AS through erythroid cell differentiation using qRT-PCR. CD34+ HSC cells from 6 healthy donors were induced to differentiate into erythrocytes by addition of erythropoietin during 12 days. We observed that LEF1-AS is modulated during erythroid differentiation. It was significantly down-regulated during the first stages of differentiation from CD34+ HSC to erythroblast (from collection day 6 to day 8 after addition of erythropoietin, 78% mean reduction, P<0.0001) and it was up-regulated at the end-point of collection, day 12 (not significant). Lef1 coding gene displayed a similar expression pattern, consistent with previous reports of Lef1 expression during erythroid maturation (Edmaier et al Leukemia 2014). To explore a possible regulatory role of LEF1-AS, we cloned and over-expressed the transcript in KG1 CD34+ leukemia cell line. Transient over-expression of Lef1-AS led to a significant up-regulation of Lef1 gene (22% increase, P<0.05). We also observed an increase in cell viability (19% increase P<0.05), measured by MTT, which is consistent with the up-regulation of LEF1, a pro-proliferative and anti-apoptotic transcription factor. Our preliminary results from over-expressing LEF1-AS in CD34+ HSCs suggest a similar regulatory effect of LEF1-AS upon its coding counterpart, LEF1. Since aberrant expression of LEF1 is known to disrupt normal differentiation of CD34+ cells, LEF1-AS could potentially affect differentiation through the modulation of LEF1 coding gene. Our results reveal LEF1-AS transcript as a novel player in hematopoiesis and hematologic malignancy. Disclosures No relevant conflicts of interest to declare.
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Cabiati, Manuela, Martina Fontanini, Manuel Giacomarra, Gianfranco Politano, Emioli Randazzo, Diego Peroni, Giovanni Federico, and Silvia Del Ry. "Screening and Identification of Putative Long Non-Coding RNA in Childhood Obesity: Evaluation of Their Transcriptional Levels." Biomedicines 10, no. 3 (February 23, 2022): 529. http://dx.doi.org/10.3390/biomedicines10030529.
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Background and Methods: Long non-coding RNAs (LncRNAs) and microRNAs are involved in the pathogenesis of obesity, a multifactorial disease that is characterized by inflammation, cardiometabolic complications, and increased cancer risk among other co-morbidities. The up/down regulation of LncRNAs and microRNAs may play an important role in this condition to identify new diagnostic/prognostic markers. The aim of the study was to identify circulating inflammatory LncRNAs in obese adolescents (n = 54) and to evaluate whether their expression behaved differently compared to normal-weight adolescents (n = 26). To have a more complete insight, the expression of some circulating miRNAs that are linked to obesity (miR-33a, miR-223, miR-142, miR-199a, miR-181a, and miR-4454) were also analyzed. Results: LncRNAs and miRNAs were extracted simultaneously from plasma samples and amplified by Real-Time PCR. Among the 86 LncRNAs that were analyzed with custom pre-designed plates, only four (RP11-347E10.1, RP11-10K16.1, LINC00657, and SNHG12) were amplified in both normal-weight and obese adolescents and only SNHG12 showed significantly lower expression compared to the normal-weight adolescents (p = 0.026). Circulating miRNAs showed a tendency to increase in obese subjects, except for miR-181a expression. LncRNAs and miRNAs correlated with some clinical and metabolic parameters. Conclusions: Our results suggest the importance of these new biomarkers to better understand the molecular mechanisms of childhood obesity and its metabolic disorder.
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Song, Yichen, Zhiying Wang, Lewei He, Feidi Sun, Beilei Zhang, and Fu Wang. "Dysregulation of Pseudogenes/lncRNA-Hsa-miR-1-3p-PAICS Pathway Promotes the Development of NSCLC." Journal of Oncology 2022 (August 30, 2022): 1–22. http://dx.doi.org/10.1155/2022/4714931.
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Objective. Non-small cell lung cancer (NSCLC) explains about 80 percent of whole lung cancers, and its 5-year survival rate is impoverished, as when people are first diagnosed, 68% of whom are identified at a dangerous stage. The molecular mechanisms of NSCLC are still being explored. Methods. GSE18842 and GSE19804 were exerted to scan for diversely expressed genes (DEGs) in NSCLC, and then we used GEPIA for the validation of DEGs expression. The prognostic values were determined through Kaplan–Meier analysis. Three target prediction databases indicated potential microRNAs (miRNAs), while miRNet predicted hsa-miR-1-3p′s upstream long non-coding RNAs (lncRNAs) and pseudogenes. UALCAN was utilized to identify the co-expressed genes of PAICS, while enrichment analysis on them was managed with Enrichr. Results. We initially found that the gene expression level of cyclin B1 (CCNB1), cyclin-dependent kinases1 (CDK1), and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) had a notable increase in NSCLC. We predicted 6, 10, and 7 microRNAs to target CCNB1, CDK1, and PAICS, respectively. Among miRNA-mRNA (microRNA-messenger RNA) pairs, we deduced that the hsa-miR-1-PAICS axis was the most potential one to inhibit the occurrence of NSCLC. We also noted that the hsa-miR-1-3p-PAICS axis participated in regulating the process of mitosis with mechanical functions. Moreover, we identified 5 pseudogenes and 33 long non-coding RNAs (lncRNAs) that might inhibit the hsa-miR-1-3p-PAICS axis in NSCLC. Conclusions. The pseudogene/lncRNA-hsa-miR-1-3p-PAICS is very important in NSCLC on the basis of this study, thus providing us with effective treatments and promising biomarkers for the diagnosis of NSCLC.
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Gokulnath, Priyanka, Tiziana de Cristofaro, Ichcha Manipur, Tina Di Palma, Amata Amy Soriano, Mario Rosario Guarracino, and Mariastella Zannini. "Long Non-Coding RNA HAND2-AS1 Acts as a Tumor Suppressor in High-Grade Serous Ovarian Carcinoma." International Journal of Molecular Sciences 21, no. 11 (June 5, 2020): 4059. http://dx.doi.org/10.3390/ijms21114059.
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Long non-coding RNAs (lncRNAs) are increasingly being identified as crucial regulators in pathologies like cancer. High-grade serous ovarian carcinoma (HGSC) is the most common subtype of ovarian cancer (OC), one of the most lethal gynecological malignancies. LncRNAs, especially in cancers such as HGSC, could play a valuable role in diagnosis and even therapy. From RNA-sequencing analysis performed between an OC cell line, SKOV3, and a Fallopian Tube (FT) cell line, FT194, an important long non-coding RNA, HAND2 Anti sense RNA 1 (HAND2-AS1), was observed to be significantly downregulated in OCs when compared to FT. Its downregulation in HGSC was validated in different datasets and in a panel of HGSC cell lines. Furthermore, this study shows that the downregulation of HAND2-AS1 is caused by promoter hypermethylation in HGSC and behaves as a tumor suppressor in HGSC cell lines. Since therapeutic relevance is of key importance in HGSC research, for the first time, HAND2-AS1 upregulation was demonstrated to be one of the mechanisms through which HDAC inhibitor Panobinostat could be used in a strategy to increase HGSC cells’ sensitivity to chemotherapeutic agents currently used in clinical trials. To unravel the mechanism by which HAND2-AS1 exerts its role, an in silico mRNA network was constructed using mRNAs whose expressions were positively and negatively correlated with this lncRNA in HGSC. Finally, a putative ceRNA network with possible miRNA targets of HAND2-AS1 and their mRNA targets was constructed, and the enriched Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified.
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Xiao, Jia, Yi Lv, Fujun Jin, Yingxia Liu, Yi Ma, Yongjia Xiong, Lei Liu, et al. "LncRNA HANR Promotes Tumorigenesis and Increase of Chemoresistance in Hepatocellular Carcinoma." Cellular Physiology and Biochemistry 43, no. 5 (2017): 1926–38. http://dx.doi.org/10.1159/000484116.
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Background/Aims: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. Methods: In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. Results: HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3β in HCC. Conclusion: Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future.
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Biswas, Saumik, Marie Sarabusky, and Subrata Chakrabarti. "Diabetic Retinopathy, lncRNAs, and Inflammation: A Dynamic, Interconnected Network." Journal of Clinical Medicine 8, no. 7 (July 14, 2019): 1033. http://dx.doi.org/10.3390/jcm8071033.
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Diabetic retinopathy (DR) is reaching epidemic levels globally due to the increase in prevalence of diabetes mellitus (DM). DR also has detrimental effects to quality of life, as it is the leading cause of blindness in the working-age population and the most common cause of vision loss in individuals with DM. Over several decades, many studies have recognized the role of inflammation in the development and progression of DR; however, in recent years, accumulating evidence has also suggested that non-coding RNAs, especially long non-coding (lncRNAs), are aberrantly expressed in diabetes and may play a putative role in the development and progression of DR through the modulation of gene expression at the transcriptional, post-transcriptional, or epigenetic level. In this review, we will first highlight some of the key inflammatory mediators and transcription factors involved in DR, and we will then introduce the critical roles of lncRNAs in DR and inflammation. Following this, we will discuss the implications of lncRNAs in other epigenetic mechanisms that may also contribute to the progression of inflammation in DR.
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Wehida, Nadine, Wafaa Abdel-Rehim, Hazem El Mansy, Ahmed Karmouty, and Maher A. Kamel. "A Panel of Circulating Non-Coding RNAs in the Diagnosis and Monitoring of Therapy in Egyptian Patients with Breast Cancer." Biomedicines 11, no. 2 (February 15, 2023): 563. http://dx.doi.org/10.3390/biomedicines11020563.
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Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC.
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Lopes, Maria Fernanda da Silva, Juliana de Souza Felix, Natália Francisco Scaramele, Mariana Cordeiro Almeida, Amanda de Oliveira Furlan, Jéssica Antonini Troiano, Flávia Regina Florêncio de Athayde, and Flávia Lombardi Lopes. "Co-expression analysis of lncRNA and mRNA identifies potential adipogenesis regulatory non-coding RNAs involved in the transgenerational effects of tributyltin." PLOS ONE 18, no. 2 (February 3, 2023): e0281240. http://dx.doi.org/10.1371/journal.pone.0281240.
Full textAbstract:
The obesity epidemic is considered a global public health crisis, with an increase in caloric intake, sedentary lifestyles and/or genetic predispositions as contributing factors. Although the positive energy balance is one of the most significant causes of obesity, recent research has linked early exposure to Endocrine-Disrupting Chemicals (EDCs) such as the obesogen tributyltin (TBT) to the disease epidemic. In addition to their actions on the hormonal profile, EDCs can induce long-term changes in gene expression, possibly due to changes in epigenetic patterns. Long non-coding RNAs (lncRNAs) are epigenetic mediators that play important regulatory roles in several biological processes, through regulation of gene transcription and/or translation. In this study, we explored the differential expression of lncRNAs in gonadal white adipose tissue samples from adult male C57BL/6J F4 generation, female C57BL/6J offspring exposed (F0 generation) to 50 nM TBT or 0.1% DMSO (control of vehicle) via drinking water provided during pregnancy and lactation, analyzing RNA-seq data from a publicly available dataset (GSE105051). A total of 74 lncRNAs were differentially expressed (DE), 22 were up-regulated and 52 were down-regulated in the group whose F4 ancestor was exposed in utero to 50nM TBT when compared to those exposed to 0.1% DMSO (control). Regulation of DE lncRNAs and their potential partner genes in gonadal white adipose tissue of mice ancestrally exposed to EDC TBT may be related to the control of adipogenesis, as pathway enrichment analyses showed that these gene partners are mainly involved in the metabolism of lipids and glucose and in insulin-related pathways, which are essential for obesity onset and control.