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1
Jongen-Lavrencic, Mojca, Su Ming Sun, Menno K. Dijkstra, Peter J. M. Valk, and Bob Löwenberg. "MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia." Blood 111, no. 10 (May 15, 2008): 5078–85. http://dx.doi.org/10.1182/blood-2008-01-133355.
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Abstract Acute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that show variable expression during myeloid differentiation. MicroRNA expression in marrow blasts in 215 cases of newly diagnosed and (cyto)genetically defined AML was assessed using quantitative reverse-transcription–polymerase chain reaction (RT-PCR) for 260 human microRNAs. In the same series, mRNA gene expression profiles were established, allowing a direct comparison between microRNA and mRNA expression. We show that microRNA expression profiling following unsupervised analysis reveals distinctive microRNA signatures that correlate with cytogenetic and molecular subtypes of AML (ie, AMLs with t(8;21), t(15;17), inv(16), NPM1, and CEBPA mutations). Significantly differentially expressed microRNAs for genetic subtypes of AML were identified. Specific microRNAs with established oncogenic and tumor suppressor functions, such as microRNA-155, microRNA-21, and let-7, appear to be associated with particular subtypes. Combinations of selected sets of microRNAs could predict cytogenetically normal AML with mutations in the genes of NPM1 and CEBPA and FLT3-ITD with similar accuracy as mRNA probe set combinations defined by gene expression profiling. MicroRNA expression apparently bears specific relationships to the heterogeneous pathobiology of AML. Distinctive microRNA signatures appear of potential value in the clinical diagnosis of AML.
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Kiseleva, Y. Y., K. G. Ptitsyn, S. P. Radko, V. G. Zgoda, and A. I. Archakov. "Digital droplet PCR - a prospective technological approach to quantitative profiling of microRNA." Biomeditsinskaya Khimiya 62, no. 4 (2016): 403–10. http://dx.doi.org/10.18097/pbmc20166204403.
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MicroRNA is a special type of regulatory molecules governing gene expression. Circulating microRNAs found in blood and other biological fluids are considered today as potential biomarkers of human pathology. Presently, quantitative alterations of particular microRNAs are revealed for a large number of oncological diseases and other disorders. The recently emerged method of digital droplet PCR (ddPCR) possesses a number of advantages making this method the most suitable for verification and validation of perspective microRNA markers of human pathologies. Among these advantages are the high accuracy and reproducibility of microRNA quantification as well as the capability to directly measure the absolute number of microRNA copies with the large dynamic range and a high throughput. The paper reviews microRNA biogenesis, the origin of circulating microRNAs, and methods used for their quantification. The special technical features of ddPCR, which make it an attractive method both for studying microRNAs as biomarkers of human pathologies and for basic research devoted to aspects of gene regulation by microRNA molecules, are also discussed.
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Wang, Xiaoxia, Chun Song, Xiao Zhou, Xiaorui Han, Jun Li, Zengwu Wang, Haibao Shang, Yuli Liu, and Huiqing Cao. "Mitochondria Associated MicroRNA Expression Profiling of Heart Failure." BioMed Research International 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/4042509.
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Heart failure (HF) is associated with mitochondrial dysfunction and energy metabolism impairment. MicroRNAs are implicated in the development of heart failure. However, the mitochondria enriched microRNA during heart failure remains elusive. Here, we generated a pressure overload-induced early and late stage heart failure model at 4 weeks and 8 weeks following transverse aortic constriction (TAC) in mice. We found that expression of mitochondrion protein COX4 was highly enriched in isolated mitochondria from cardiac tissues while GAPDH could hardly be detected. Furthermore, small RNA sequencing for mitochondria RNAs from failing hearts was performed. It was found that 69 microRNAs were upregulated and 2 were downregulated in early heart failure, while 16 microRNAs were upregulated and 6 were downregulated in late heart failure. 15 microRNA candidates were measured in both mitochondria and total cardiac tissues of heart failure by real-time PCR. MiR-696, miR-532, miR-690, and miR-345-3p were enriched in mitochondria from the failing heart at early stage. Bioinformatics analysis showed that mitochondria enriched microRNAs in HF were associated with energy metabolism and oxidative stress pathway. For the first time, we demonstrated microRNAs were enriched in mitochondria during heart failure, which established a link between microRNA and mitochondrion in heart failure.
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Liu, Xiqiang, Zugen Chen, Jinsheng Yu, James Xia, and Xiaofeng Zhou. "MicroRNA Profiling and Head and Neck Cancer." Comparative and Functional Genomics 2009 (2009): 1–11. http://dx.doi.org/10.1155/2009/837514.
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Head and neck/oral cancer (HNOC) is a devastating disease. Despite advances in diagnosis and treatment, mortality rates have not improved significantly over the past three decades. Improvement in patient survival requires a better understanding of the disease progression so that HNOC can be detected early in the disease process and targeted therapeutic interventions can be deployed. Accumulating evidence suggests that microRNAs play important roles in many human cancers. They are pivotal regulators of diverse cellular processes including proliferation, differentiation, apoptosis, survival, motility, and morphogenesis. MicroRNA expression patterns may become powerful biomarkers for diagnosis and prognosis of HNOC. In addition, microRNA therapy could be a novel strategy for HNOC prevention and therapeutics. Recent advances in microRNA expression profiling have led to a better understanding of the cancer pathogenesis. In this review, we will survey recent technological advances in microRNA profiling and their applications in defining microRNA markers/targets for cancer prediction, diagnostics, treatment, and prognostics. MicroRNA alterations that consistently identified in HNOC will be discussed, such as upregulation of miR-21, miR-31, miR-155, and downregulation of miR-26b, miR-107, miR-133b, miR-138, and miR-139.
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Chen, Zujian, Tianwei Yu, Robert J. Cabay, Yi Jin, Ishrat Mahjabeen, Xianghong Luan, Lei Huang, Yang Dai, and Xiaofeng Zhou. "miR-486-3p, miR-139-5p, and miR-21 as Biomarkers for the Detection of Oral Tongue Squamous Cell Carcinoma." Biomarkers in Cancer 9 (January 2017): 1179299X1700900. http://dx.doi.org/10.1177/1179299x1700900001.
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Oral tongue squamous cell carcinoma (TSCC) is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to test the feasibility of performing the microRNA profiling analysis on archived TSCC specimens and to assess the potential diagnostic utility of the identified microRNA biomarkers for the detection of TSCC. TaqMan array-based microRNA profiling analysis was performed on 10 archived TSCC samples and their matching normal tissues. A panel of 12 differentially expressed microRNAs was identified. Eight of these differentially expressed microRNAs were validated in an independent sample set. A random forest (RF) classification model was built with miR-486-3p, miR-139-5p, and miR-21, and it was able to detect TSCC with a sensitivity of 100% and a specificity of 86.7% (overall error rate = 6.7%). As such, this study demonstrated the utility of the archived clinical specimens for microRNA biomarker discovery. The feasibility of using microRNA biomarkers (miR-486-3p, miR-139-5p, and miR-21) for the detection of TSCC was confirmed.
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Segura-Wang, Maia, Bertrand Grenier, Suzana Ilic, Ursula Ruczizka, Maximiliane Dippel, Moritz Bünger, Matthias Hackl, and Veronika Nagl. "MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers." International Journal of Molecular Sciences 22, no. 21 (November 7, 2021): 12043. http://dx.doi.org/10.3390/ijms222112043.
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Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses. Piglets received uncontaminated feed or feed containing 900 µg/kg and 2500 µg/kg DON for four weeks, followed by a wash-out period. In tissue, only slight changes in microRNA expression were detected, with ssc-miR-10b being downregulated in liver of DON-exposed piglets. In serum, several microRNAs were differentially expressed upon DON exposure, four of which were validated by qPCR (ssc-miR-16, ssc-miR-128, ssc-miR-451, ssc-miR-205). The serum microRNA response to DON increased over time and declined after removal of contaminated diets. Receiver operating curve analyses for individual microRNAs were significant, and a combination of the four microRNAs increased the predictive capacity for DON exposure. Predicted microRNA target genes showed enrichment of several pathways including PIK3-AKT, Wnt/β-catenin, and adherens junctions. This study gives, for the first time, a comprehensive view of the porcine microRNA response to DON, providing a basis for future research on microRNAs as biomarkers for mycotoxins.
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Adamia, Sophia, Samir B. Amin, Cheng Li, Christopher J. Patterson, Herve AvetLoiseau, Stephane Minvielle, Philippe Moreau, Kenneth C. Anderson, Nikhil C. Munshi, and Steven Treon. "High-Throughput Microrna Profiling in Patients with Waldenstrom’s Macroglobulinemia." Blood 112, no. 11 (November 16, 2008): 1704. http://dx.doi.org/10.1182/blood.v112.11.1704.1704.
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Abstract Waldenström’s macroglobulinemia (WM) is an incurable B cell malignancy characterized by the accumulation of IgM secreting clonally related bone marrow lymphoplasmacytic cells (LPC) including CD19+ B-cells and CD138+ plasma cells. Despite intense research efforts, the pathogenetic basis for this disease remains to be clarified. MicroRNAs are small noncoding RNAs that regulate the expression of protein-coding genes by inducing translational inhibition and through cleavage of targeted transcripts by partial or complete base pairing. We therefore evaluated the expression of 384 microRNAs in CD19+ and CD138+ sorted bone marrow lymphoplasmacytic from 13 untreated WM patients, and compared their expression profiling to analogous lymphoplasmacytic cells taken from the bone marrows of 13 healthy donors. Data obtained from microRNA arrays was analyzed using SDS, RQ manager, R and dChip softwares. Relative expression was calculated using the comparative Ct method through RQ manager and dChip softwares. Of the 384 microRNAs evaluated in CD19+ patient cells, miR-192, -125b, -21, -155 demonstrated significant upregulation, whereas miR-181c, -572, and -650 were significantly down regulated compared to healthy donor CD19+ bone marrow cells (p<0.05). Analysis of bone marrow derived CD138+ cells from WM patients demonstrated significant upregulation in miR-192, -193b, -17-3p, -585, -148b, whereas miR-29c, -155, -126, -148a, -125a, -181d, -30a-3p, let-7b, let-7c were downregulated in comparison to healthy donor CD138+ bone marrow cells (p<0.05). Importantly, characterization of the modulated microRNAs found in these studies demonstrated a critical role in growth and survival pathways through modulation of several genes including HOX, BCL-2 and c-myc. Taken together, these studies demonstrate significant differences in microRNA expression between comparable WM and healthy donor lymphoplasmacytic cell populations, and identify aberrancies in microRNAs with a pivotal role in the growth and survival of B-cells.
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Pimentel, Fernando, Patricia Bonilla, Yashwanth G. Ravishankar, Alec Contag, Nimish Gopal, Sarah LaCour, Trenton Lee, and Angelika Niemz. "Technology in MicroRNA Profiling." Journal of Laboratory Automation 20, no. 5 (October 2015): 574–88. http://dx.doi.org/10.1177/2211068214561788.
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Munker, Reinhold, and George A. Calin. "MicroRNA profiling in cancer." Clinical Science 121, no. 4 (April 20, 2011): 141–58. http://dx.doi.org/10.1042/cs20110005.
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The diagnosis of cancer has undergone major changes in the last 40 years. Once based purely on morphology, diagnosis has come to incorporate immunological, cytogenetic and molecular methods. Many cancers, especially leukaemias, are now defined by molecular markers. Gene expression profiling based on mRNA has led to further refinement of the classification and diagnosis of cancer. More recently, miRNAs (microRNAs), among other small non-coding RNA molecules, have been discovered and found to be major players in cell biology. miRNAs, having both oncogenic and tumour-suppressive functions, are dysregulated in many types of cancer. miRNAs also interfere with metastasis, apoptosis and invasiveness of cancer cells. In the present review, we discuss recent advances in miRNA profiling in human cancer. We discuss both frequent and rare tumour types and give an outlook on future developments.
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Iorio, Marilena V., and Carlo M. Croce. "MicroRNAs in Cancer: Small Molecules With a Huge Impact." Journal of Clinical Oncology 27, no. 34 (December 1, 2009): 5848–56. http://dx.doi.org/10.1200/jco.2009.24.0317.
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Every cellular process is likely to be regulated by microRNAs, and an aberrant microRNA expression signature is a hallmark of several diseases, including cancer. MicroRNA expression profiling has indeed provided evidence of the association of these tiny molecules with tumor development and progression. An increasing number of studies have then demonstrated that microRNAs can function as potential oncogenes or oncosuppressor genes, depending on the cellular context and on the target genes they regulate. Here we review our current knowledge about the involvement of microRNAs in cancer and their potential as diagnostic, prognostic, and therapeutic tools.
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Adamia, S., H. Avet-Loiseau, S. B. Amin, P. Moreau, S. S. Minvielle, S. Treon, C. Li, K. C. Anderson, and N. Munshi. "Clinical and biological significance of microRNA profiling in patients with myeloma." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8539. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8539.
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8539 MicroRNA, a small endogenous RNA regulating specific expressed gene function has been implicated in normal biological processes as well as in malignant transformation. Here we have investigated the role of microRNAs in multiple myeloma (MM) biology, and their influence on prognosis and clinical outcome. We evaluated profiles of 384 microRNAs in CD138+ MM cells from 79 patients with MM, 11 cell lines and 9 healthy donors using qRT-PCR based microRNA array. We detected significant modulation of expression of 61 microRNAs in myeloma cells compared to normal plasma cells. Unsupervised hierarchical clustering of filtered matured microRNAs, identified two major groups within the MM population (groups A and group B). Group A clustered with MM cell lines, indicating more aggressive course of disease. Within B group, second degree node, group B2, clustered with normal plasma cells indicating indolent course. The unsupervised clustering of all MM samples showed consistent change in miR-146b, -140, -145, -125a, -151, -223, -155, let-7f, indicative of a role of these microRNA in myelomagenesis; while supervised analysis of samples within groups A and B identified modulated expression of different sets of miRNAs. In group A miR585 and let-7f were upregulated 8–12 fold; in group B, all differentially expressed microRNAs were downregulated (p<0.001) compared to normal plasma cells. These modulated miRNAs target critical signaling molecules such as HOX9, c-myc, Bcl-2, SHP1 and SHP2. We further analyzed the effect of microRNA on clinical outcome. We have observed significantly superior event free and overall survival of patients in group B compared to patients ingroup A (2 yr estimated EFS 79% versus 54% respectively; p=0.05; and 2 yr estimated OS 94% versus 70% respectively; p =0.017). Functional analysis by modulating miRNAs 585, 155 and let-7f showed change in levels of predicted genes with consequent biological effect on growth and apoptosis in MM cell line. Taken together, this data identifies miRNAs as critical modulators of gene expression and signaling pathways and provides potential novel targets in MM to both understand biological behavior and for therapeutic application. No significant financial relationships to disclose.
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Martinez-Fierro, Margarita L., and Idalia Garza-Veloz. "Analysis of Circulating microRNA Signatures and Preeclampsia Development." Cells 10, no. 5 (April 24, 2021): 1003. http://dx.doi.org/10.3390/cells10051003.
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microRNAs are important regulators of cell processes and have been proposed as potential preeclampsia biomarkers. We evaluated serum microRNA expression profiling to identify microRNAs involved in preeclampsia development. Serum microRNA expression profiling was evaluated at 12, 16, and 20 weeks of gestation (WG), and at the time of preeclampsia diagnosis. Two groups were evaluated using TaqMan low-density array plates: a control group with 18 normotensive pregnant women and a case group with 16 patients who developed preeclampsia during the follow-up period. Fifty-three circulating microRNAs were differentially expressed between groups (p < 0.05). Compared with controls, hsa-miR-628-3p showed the highest relative quantity values (at 12 WG = 7.7 and at 20 WG = 3.45) and the hsa-miRs -151a-3p and -573 remained differentially expressed from 16 to 20 WG (p < 0.05). Signaling pathways including cancer-related, axon guidance, Neurotrophin, GnRH, VEGF, and B/T cell receptor, were most commonly altered. Further target gene prediction revealed that nuclear factor of activated T-cells 5 gene was included among the transcriptional targets of preeclampsia-modulated microRNAs. Specific microRNAs including hsa-miRs -628-3p, -151a-3p, and -573 were differentially expressed in serum of pregnant women before they developed preeclampsia compared with controls and their participation in the preeclampsia development should be considered.
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de Leeuw, David C., Fedor Denkers, Gerrit J. Schuurhuis, Gert J. Ossenkoppele, and Linda Smit. "MicroRNA Expression Profiling of Hematopoietic and Leukemic Stem Cells in Acute Myeloid Leukemia,." Blood 118, no. 21 (November 18, 2011): 3999. http://dx.doi.org/10.1182/blood.v118.21.3999.3999.
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Abstract Abstract 3999 Treatment of acute myeloid leukemia (AML) patients with chemotherapy results in complete remission in up to 80% of patients. However, 50% of patients experience a relapse which is thought to be caused by the survival of a population of dormant leukemic stem cells (LSC) that are resistant to chemotherapy. These LSC are responsible for the initiation, maintenance and relapse of AML and eradication of these cells is therefore necessary to cure AML patients. LSC and normal hematopoietic stem cells (HSC) coexist in AML bone marrow and future LSC-specific therapy relies on identification of new targets differentiating normal from malignant stem cells. Our major aim is the development of novel LSC specific microRNA-based therapeutic strategies by identification of microRNAs differentially expressed and functioning in the AML LSC and HSC critical for self-renewal and/or therapy response. We want to use microRNA expression profiling of LSC and HSC within one AML bone marrow sample to identify LSC-specific targets. MicroRNAs are non-coding single stranded RNAs of 21–25 nucleotides. They regulate gene expression by promoting degradation of mRNA or repressing its translation. MicroRNAs are critical regulators involved in various cell processes, including differentiation, proliferation and apoptosis. Whereas a few studies have been performed comparing microRNA expression of LSC with healthy donor HSC, which is not identical to AML HSC, no such studies have been performed comparing LSC with HSC both present in the same AML bone marrow. This is now possible with the by us identified markers/parameters discriminating LSC from HSC present within one AML bone marrow sample. Recently we have shown that the small portion of healthy HSC in the CD34+CD38- compartment of AML patients can be identified and purified by using aldehyde dehydrogenase activity. CD34+CD38- stem cells with high aldehyde dehydrogenase activity have no molecular and immunophenotypical aberrancies suggesting a normal phenotype (HSC). Whereas CD34+CD38- stem cells with low aldehyde dehydrogenase activity, harbor leukemia associated aberrancies. This shows that normal HSC have high aldehyde dehydrogenase activity as compared to LSC residing in the same AML bone marrow. We have studied the microRNA expression profile of AML LSC and normal HSC, discriminated by aldehyde dehydrogenase activity, within the patient's bone marrow in order to find microRNAs differentially expressed in LSC and HSC. Besides this, we have studied the microRNA expression profile in the more differentiated blast population of the AML bone marrow. Cells from the bone marrow of AML patients were purified by flow cytometry based on surface marker expression and aldehyde dehydrogenase activity. Leukemic blasts by being CD34+, LSC by being CD34+CD38-ALDHlow and HSC by being CD34+CD38-ALDHhigh. RNA was isolated from the various cell populations and microRNA expression was studied using Agilent microRNA microarrays. Most microRNAs show similar levels of expression in the different cell compartments. However, expression of miR-126 was significantly enhanced while the tumorsupressors miR-451 and miR-34a were downregulated in LSC as compared to leukemic blasts. Comparison of the microRNA expression profile of LSC and HSC showed that expression of miR-21, miR-181a/b and the cluster miR-221/222 was significantly upregulated while others, such as miR-10a and miR-451 were downregulated. In conclusion, we have identified several microRNAs that are differentially expressed between leukemic blasts, LSC and HSC. Some of these microRNAs have already been linked to stem cell properties such as senescence or chemotherapy resistance while others have unknown functions. Our findings might give more insights in the mechanisms regulating LSC and are important for understanding processes like leukemogenesis and relapse. Furthermore, these microRNAs might in de future prove to be valuable targets for LSC directed therapy while saving the normal HSC. Disclosures: No relevant conflicts of interest to declare.
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Bouyssou, Juliette Marie Charlotte, Yosra Aljawai, Amir Yosef, Salomon Manier, Ragyie Rawal, Katsutoshi Kokubun, Adriana Perilla Glen, et al. "Profiling of Circulating Exosomes in Patients with Waldenström Macroglobulinemia." Blood 128, no. 22 (December 2, 2016): 2940. http://dx.doi.org/10.1182/blood.v128.22.2940.2940.
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Abstract Introduction. Waldenström Macroglobulinemia (WM) is a low- grade B-cell lymphoma with a heterogeneous clinical presentation. In many patients, the diagnosis is preceded by an asymptomatic precursor state of IgM monoclonal gammopathy of undetermined significance (MGUS) and smoldering WM. However, little is known about the mechanisms involved in the progression from asymptomatic WM to symptomatic WM. Exosomes are small vesicles secreted by cells that enable the transfer of nucleic acids, proteins and lipids between distant cells in the organism. Because of the active role of exosomes in promoting tumor growth and metastasis, we investigated the microRNA content of circulating exosomes in patients at different stages of WM in order to identify possible markers of progression. Methods.We isolated exosomes by ultracentrifugation from the peripheral blood plasma of 101 patients with WM and 10 normal donors. The WM cases included 7 patients with IgM MGUS, 42 patients with smoldering WM and 52 patients with symptomatic WM. We first profiled microRNAs from the exosomes of 14 patients and 5 normal controls using the TaqMan Array Human MicroRNA A Card (Thermo Fisher Scientific) which enables the quantitation of 377 human microRNAs. Exosomes from an additional group of 14 individuals (2 normal donors, 8 patients with asymptomatic WM and 4 patients with symptomatic WM) were profiled with the Oncology Panel of the Firefly Multiplex Circulating miRNA Assay (Abcam), which measures the expression level of 68 different human microRNAs. Following these analyses, a group of 33 microRNAs deregulated between patients' groups was selected and a custom microRNA panel was built to allow quantitation of these microRNAs with the Firefly Multiplex Circulating miRNA Assay (Abcam). The level of expression of these 33 microRNAs was measured in a group of 80 individuals comprised of healthy controls (n=8), patients with asymptomatic WM including IgM MGUS and smoldering WM (n=34) and patients with previously untreated symptomatic WM (n=11), relapsed WM (n=21) and refractory WM (n=6). Additionally, exosomes were imaged using electron microscopy with immunogold labeling for the detection of the exosome-specific receptors CD63 and CD81. Results. Imaging with electron microscopy showed vesicles with a size ranging from 50 to 150 nm and expressing CD63 and CD81, thus validating our ultracentrifugation method for exosome isolation. Among the 33 microRNAs analyzed, 12 were significantly deregulated between WM patients and healthy controls (P<0.05), of which 6 were upregulated and 6 downregulated. When comparing patients with IgM MGUS and smoldering WM to patients with symptomatic WM, the expression level of 7 microRNAs differed significantly (P<0.05), including 2 microRNAs underexpressed and 5 microRNAs overexpressed in symptomatic patients. Among the microRNAs whose expression most significantly correlated with disease progression were let-7d, miR-93-5p, miR-103a-3p, miR-192-5p and miR-320b. Conclusion. The microRNA content of circulating exosomes differs at different stages of WM progression. This could potentially be used to further define prognostic markers of progression in patients with WM, specifically progression from asymptomatic WM to overt WM. The study of these deregulated microRNAs' effect on in vitro and in vivo WM models can help us gain insights on mechanisms of disease progression in WM. Disclosures Castillo: Janssen: Honoraria; Abbvie: Research Funding; Pharmacyclics: Honoraria; Biogen: Consultancy; Otsuka: Consultancy; Millennium: Research Funding. Treon:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy. Roccaro:Takeda Pharmaceutical Company Limited: Honoraria. Hermine:Novartis: Research Funding; AB science: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Alexion: Research Funding; Celgene: Research Funding. Ghobrial:Noxxon: Honoraria; Celgene: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria.
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Mouritzen, Peter, Søren Jensby Nielsen, Maria Wrang Teilum, Thorarinn Blondal, Ditte Andreasen, and Niels Tolstrup. "MicroRNA in biofluids—Robust biomarkers for disease, toxicology, or injury studies: The case of minimally invasive colorectal cancer detection." Journal of Clinical Oncology 30, no. 30_suppl (October 20, 2012): 20. http://dx.doi.org/10.1200/jco.2012.30.30_suppl.20.
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20 Background: MicroRNAs function as post-transcriptional regulators of gene expression. Their high relative stability in common clinical source materials (FFPE blocks, plasma, serum, urine, saliva, etc.) and the ability of microRNA expression profiles to accurately classify discrete tissue types and specific disease states have positioned microRNAs as promising new biomarkers for diagnostic application. Furthermore microRNAs have been shown to be rapidly released from tissues into the circulation with the development of pathology. Methods: Thousands of biofluid samples were profiled including blood derived plasma/serum and urine using a genome-wide LNA-based microRNA qPCR platform, which has unparalleled sensitivity and robustness even in biofluids with extremely low microRNA levels. Only a single RT reaction is required to conduct full miRNome profiling thereby facilitating high-throughput profiling without the need for pre-amplification. Results: Normal reference ranges for circulating microRNAs were determined in several biofluids, allowing development of qPCR arrays containing only relevant microRNA subsets present in various biofluids together with tissue specific microRNA markers. Procedures were developed to control pre-analytical variables, for quality checking and qualifying biofluid samples in particular serum and plasma but also urine and other biofluids. An extensive QC system was implemented in order to secure technical excellence and reveal any unwanted bias in the dataset. We currently screen and validate microRNAs biomarkers for cancer with the aim of developing minimal invasive tests to be applied in early detection population screens. Conclusions: The qPCR panels support development of robust biomarkers in disease, toxicology, and injury studies. We will demonstrate how panels may be quickly and robustly applied in biomarker discovery/validation projects using the specific case early detection of colorectal cancer in blood. Close attention is required on pre-analytical parameters. Hemolysis and cellular contamination affect miRNA profiles in biofluids and control is required.
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Shah, Manasvi S., Scott L. Schwartz, Chen Zhao, Laurie A. Davidson, Beiyan Zhou, Joanne R. Lupton, Ivan Ivanov, and Robert S. Chapkin. "Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemo-protective diet." Physiological Genomics 43, no. 10 (May 2011): 640–54. http://dx.doi.org/10.1152/physiolgenomics.00213.2010.
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We have recently demonstrated that nutritional bioactives (fish oil and pectin) modulate microRNA molecular switches in the colon. Since integrated analysis of microRNA and mRNA expression at an early stage of colon cancer development is lacking, in this study, four computational approaches were utilized to test the hypothesis that microRNAs and their posttranscriptionally regulated mRNA targets, i.e., both total mRNAs and actively translated mRNA transcripts, are differentially modulated by carcinogen and diet treatment. Sprague-Dawley rats were fed diets containing corn oil ± fish oil with pectin ± cellulose and injected with azoxymethane or saline (control). Colonic mucosa was assayed at an early time of cancer progression, and global gene set enrichment analysis was used to obtain those microRNAs significantly enriched by the change in expression of their putative target genes. In addition, cumulative distribution function plots and functional network analyses were used to evaluate the impact of diet and carcinogen combination on mRNA levels induced via microRNA alterations. Finally, linear discriminant analysis was used to identify the best single-, two-, and three-microRNA combinations for classifying dietary effects and colon tumor development. We demonstrate that polysomal profiling is tightly related to microRNA changes when compared with total mRNA profiling. In addition, diet and carcinogen exposure modulated a number of microRNAs (miR-16, miR-19b, miR-21, miR26b, miR27b, miR-93, and miR-203) linked to canonical oncogenic signaling pathways. Complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels.
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Dahiya, Neetu, and Patrice J. Morin. "MicroRNAs in ovarian carcinomas." Endocrine-Related Cancer 17, no. 1 (March 2010): F77—F89. http://dx.doi.org/10.1677/erc-09-0203.
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The molecular mechanisms involved in epithelial ovarian cancer initiation and progression are just beginning to be elucidated. In particular, it has become evident that microRNAs (miRNAs or miRs), a class of molecules that post-transcriptionally regulate gene expression, play a major role in ovarian tumorigenesis. Several microRNA profiling studies have identified changes in microRNA patterns that take place during ovarian cancer development. While most deregulated microRNAs are down-regulated in cancer, and may therefore act as tumor suppressors, others are elevated and may represent novel oncogenes in this disease. A number of microRNAs identified as aberrantly expressed in ovarian carcinoma have been shown to have important functional roles in cancer development and may therefore represent targets for therapy. In addition, some of the microRNA patterns may have prognostic significance. The identification of functional targets represents a major hurdle in our understanding of microRNA function in ovarian carcinoma, but significant progress is being made. It is hoped that a better understanding of the microRNA expression and roles in ovarian cancer may provide new avenues for the detection, diagnosis, and therapy of this deadly disease.
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Liu, Yuan, and Quanzhong Liu. "MicroRNAs as regulatory elements in psoriasis." Open Medicine 11, no. 1 (January 1, 2016): 336–40. http://dx.doi.org/10.1515/med-2016-0063.
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AbstractPsoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.
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Jacobs, Cassandra L., Anand S. Lagoo, Raj C. Dash, Adekunle Raji, Andrew M. Evens, Jane N. Winter, Leo I. Gordon, et al. "MicroRNAs Distinguish Burkitt Lymphoma from the Molecular Subsets of Diffuse Large B Cell Lymphoma." Blood 112, no. 11 (November 16, 2008): 3353. http://dx.doi.org/10.1182/blood.v112.11.3353.3353.
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Abstract Background: Burkitt lymphoma (BL) is a highly aggressive lymphoma that can be cured in up to 80% of patients when treated with intensive multi-agent chemotherapy. The distinction between BL and diffuse large B-cell lymphoma (DLBCL) is critical because there are important differences in their clinical management. However, the distinction can be difficult because of an overlap between DLBCL and BL in morphology, immunophenotype and cytogenetics. Previous work has shown that gene expression profiling can distinguish these entities with a high degree of certainty. Our previous work has demonstrated that microRNAs play a direct role in regulating key transcription factors in normal and malignant B cells. We investigated whether microRNA expression could be used to reliably distinguish BL from DLBCL. Methods: Biopsy samples were collected from 104 patients with a diagnosis of either sporadic BL (N=25) or DLBCL (N=79). All cases were reviewed for pathology diagnosis and profiled for microRNA expression using microarrays. Using the 30 most highly differentially expressed microRNAs with the highest t-statistic, we applied singular value decomposition to identify the 10 most predictive microRNAs. Using those 10 microRNAs, we constructed a Bayesian predictor to distinguish BL from DLBCL. The predictor performance was tested using leave-one-out cross-validation. We further applied gene expression profiling to 52 cases of DLBCL to identify the molecular subsets of DLBCL: activated B cell type and germinal center B cell type DLBCL. We constructed a Bayesian predictor to distinguish these molecular subsets based upon their gene expression. A separate predictor was created from the microRNA profiles of these DLBCL subsets and tested using leave-one-out cross-validation. In order to understand the effects of lineage-specific microRNAs in B cell lymphomas, we applied FACS-sorting to isolate mature B cell subsets including naïve B cells, germinal center B cells, plasma cells and memory cells. We compared the microRNAs involved in germinal center differentiation to those expressed highly in Burkitt lymphoma. Results: The predictor constructed based on microRNA expression was 90% accurate in distinguishing Burkitt lymphoma from DLBCL, using pathology diagnosis as the standard. The microRNA-based predictor was also over 90% accurate in the distinction of the molecular subsets of DLBCL, compared to the gold standard of gene expression-profiling. Further, we found that the Burkitt lymphoma cases consistently expressed microRNAs related to normal germinal center B cell differentiation, suggesting that they also maintain expression of B cell stage-specific microRNAs. Conclusion: This study demonstrates that the microRNA expression profiles can be used to accurately distinguish Burkitt lymphoma from DLBCL. The ability of the predictor to identify the molecular subsets of patients with DLBCL and those with BL suggests that it will be useful in the diagnosis and management of patients with Burkitt lymphoma. Further, the patterns of microRNA expression and their target genes suggests a role for microRNAs in the pathophysiology of these tumors.
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Qin, Li-Xuan. "An Integrative Analysis of microRNA and mRNA Expression–-A Case Study." Cancer Informatics 6 (January 2008): CIN.S633. http://dx.doi.org/10.4137/cin.s633.
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Background MicroRNAs are believed to play an important role in gene expression regulation. They have been shown to be involved in cell cycle regulation and cancer. MicroRNA expression profiling became available owing to recent technology advancement. In some studies, both microRNA expression and mRNA expression are measured, which allows an integrated analysis of microRNA and mRNA expression. Results We demonstrated three aspects of an integrated analysis of microRNA and mRNA expression, through a case study of human cancer data. We showed that (1) microRNA expression efficiently sorts tumors from normal tissues regardless of tumor type, while gene expression does not; (2) many microRNAs are down-regulated in tumors and these microRNAs can be clustered in two ways: microRNAs similarly affected by cancer and microRNAs similarly interacting with genes; (3) taking let-7f as an example, targets genes can be identified and they can be clustered based on their relationship with let-7f expression. Discussion Our findings in this paper were made using novel applications of existing statistical methods: hierarchical clustering was applied with a new distance measure–the co-clustering frequency–to identify sample clusters that are stable; microRNA-gene correlation profiles were subject to hierarchical clustering to identify microRNAs that similarly interact with genes and hence are likely functionally related; the clustering of regression models method was applied to identify microRNAs similarly related to cancer while adjusting for tissue type and genes similarly related to microRNA while adjusting for disease status. These analytic methods are applicable to interrogate multiple types of -omics data in general.
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Roccaro, Aldo M., Antonio Sacco, Changzhong Chen, Judith Runnels, Xavier Leleu, Feda Azab, Abdel Kareem Azab, et al. "microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia." Blood 113, no. 18 (April 30, 2009): 4391–402. http://dx.doi.org/10.1182/blood-2008-09-178228.
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AbstractMultilevel genetic characterization of Waldenström macroglobulinemia (WM) is required to improve our understanding of the underlying molecular changes that lead to the initiation and progression of this disease. We performed microRNA-expression profiling of bone marrow–derived CD19+ WM cells, compared with their normal cellular counterparts and validated data by quantitative reverse-transcription–polymerase chain reaction (qRT-PCR). We identified a WM-specific microRNA signature characterized by increased expression of microRNA-363*/-206/-494/-155/-184/-542-3p, and decreased expression of microRNA-9* (ANOVA; P < .01). We found that microRNA-155 regulates proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways. Potential microRNA-155 target genes were identified using gene-expression profiling and included genes involved in cell-cycle progression, adhesion, and migration. Importantly, increased expression of the 6 miRNAs significantly correlated with a poorer outcome predicted by the International Prognostic Staging System for WM. We further demonstrated that therapeutic agents commonly used in WM alter the levels of the major miRNAs identified, by inducing downmodulation of 5 increased miRNAs and up-modulation of patient-downexpressed miRNA-9*. These data indicate that microRNAs play a pivotal role in the biology of WM; represent important prognostic marker; and provide the basis for the development of new microRNA-based targeted therapies in WM.
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Ikeda, Sadakatsu, Sek Won Kong, Jun Lu, Egbert Bisping, Hao Zhang, Paul D. Allen, Todd R. Golub, Burkert Pieske, and William T. Pu. "Altered microRNA expression in human heart disease." Physiological Genomics 31, no. 3 (November 2007): 367–73. http://dx.doi.org/10.1152/physiolgenomics.00144.2007.
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MicroRNAs are recently discovered regulators of gene expression and are becoming increasingly recognized as important regulators of heart function. Genome-wide profiling of microRNAs in human heart failure has not been reported previously. We measured expression of 428 microRNAs in 67 human left ventricular samples belonging to control ( n = 10), ischemic cardiomyopathy (ICM, n = 19), dilated cardiomyopathy (DCM, n = 25), or aortic stenosis (AS, n = 13) diagnostic groups. miRNA expression between disease and control groups was compared by ANOVA with Dunnett's post hoc test. We controlled for multiple testing by estimating the false discovery rate. Out of 428 microRNAs measured, 87 were confidently detected; 43 were differentially expressed in at least one disease group. In supervised clustering, microRNA expression profiles correctly grouped samples by their clinical diagnosis, indicating that microRNA expression profiles are distinct between diagnostic groups. This was further supported by class prediction approaches, in which the class (control, ICM, DCM, AS) predicted by a microRNA-based classifier matched the clinical diagnosis 69% of the time ( P < 0.001). These data show that expression of many microRNAs is altered in heart disease and that different types of heart disease are associated with distinct changes in microRNA expression. These data will guide further studies of the contribution of microRNAs to heart disease pathogenesis.
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Ahmed, Atif A., Midhat S. Farooqi, Sultan S. Habeebu, Elizabeth Gonzalez, Terrie G. Flatt, Ashley L. Wilson, and Frederic G. Barr. "NanoString Digital Molecular Profiling of Protein and microRNA in Rhabdomyosarcoma." Cancers 14, no. 3 (January 21, 2022): 522. http://dx.doi.org/10.3390/cancers14030522.
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Purpose: Rhabdomyosarcoma (RMS) exhibits a complex prognostic algorithm based on histologic, biologic and clinical parameters. The embryonal (ERMS) and spindle cell-sclerosing RMS (SRMS) histologic subtypes warrant further studies due to their heterogenous genetic background and variable clinical behavior. NanoString digital profiling methods have been previously highlighted as robust novel methods to detect protein and microRNA expression in several cancers but not in RMS. Methods/Patients: To identify prognostic biomarkers, we categorized 12 ERMS and SRMS tumor cases into adverse (n = 5) or favorable (n = 7) prognosis groups and analyzed their signaling pathways and microRNA profiles. The digital spatial profiling of protein and microRNA analysis was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue using NanoString technology. Results: The detectable expression of several component members of the PI3K/AKT, MAPK and apoptosis signaling pathways was highlighted in RMS, including INPP4B, Pan-AKT, MET, Pan-RAS, EGFR, phospho-p90 RSK, p44/42 ERK1/2, BAD, BCL-XL, cleaved caspase-9, NF1, PARP and p53. Compared to cases with favorable prognosis, the adverse-prognosis tumor samples had significantly increased expression of INPP4B, which was confirmed with traditional immunohistochemistry. The analysis of microRNA profiles revealed that, out of 798 microRNAs assessed, 228 were overexpressed and 134 downregulated in the adverse prognosis group. Significant over-expression of oncogenic/tumor suppressor miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548ar-5p and miR-548y (p < 0.05) was noted in the adverse prognosis group. Conclusion: This study highlights the utility of NanoString digital profiling methods in RMS, where it can detect distinct molecular signatures with the expression of signaling pathways and microRNAs from FFPE tumor tissue that may help identify prognostic biomarkers of interest. The overexpression of INPP4B and miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548y and miR-548ar-5p may be associated with worse overall survival in ERMS and SRMS.
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Ohlsson Teague, E. M. C., V. Nisenblat, S. A. Robertson, and M. L. Hull. "506. MENSTRUAL CYCLE VARIATIONS IN PLASMA microRNA EXPRESSION PROFILES." Reproduction, Fertility and Development 21, no. 9 (2009): 106. http://dx.doi.org/10.1071/srb09abs506.
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microRNAs are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Plasma and serum microRNAs correlate closely with microRNA profiles of diseased tissue and have been explored as blood-based biomarkers for human diseases, including steroid-driven malignancies. However, reproductive steroid signalling regulates the expression of specific microRNAs and this could impact the utility of microRNA biomarkers in reproductive aged women. We hypothesised that microRNA expression profiles are altered by steroid hormone fluctuations associated with the menstrual cycle. To test this hypothesis, plasma microRNA expression was measured in healthy women at 3 stages of a 28 day menstrual cycle; ie menstrual (day 3-5), follicular (day 9–13) and implantation window/secretory phase (day 18–22). Total RNA was extracted from plasma, multiplex reverse transcription was performed, and the cDNA pre-amplified prior to expression analysis of 667 microRNAs on Taqman low density PCR arrays (n=6 women). Preliminary data shows that up to 200 microRNAs may be detected with this methodology, and that at least 14 of these are differentially expressed (fold change ≥±1.5) at follicular and secretory phase, as compared to menstrual phase. We plan to confirm these findings with standard Taqman microRNA assays (n=10 women). Our findings suggest that plasma miRNA expression profiles change over the menstrual cycle, and that this could confound microRNA-based diagnostic tests. We hope to demonstrate the most appropriate cycle phase for blood-based miRNA profiling, facilitating the development of plasma microRNA-based diagnostic tests and providing valuable information to researchers studying circulating microRNA profiles in reproductive aged women.
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Balaskas, Panagiotis, Katarzyna Goljanek-Whysall, Peter Clegg, Yongxiang Fang, Andy Cremers, Pieter Emans, Tim Welting, and Mandy Peffers. "MicroRNA Profiling in Cartilage Ageing." International Journal of Genomics 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/2713725.
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Osteoarthritis (OA) is the most common age-related joint disorder in man. MicroRNAs (miRNA), a class of small noncoding RNAs, are potential therapeutic targets for regulating molecular mechanisms in both disease and ageing. Whilst there is an increasing amount of research on the roles of miRNAs in ageing, there has been scant research on age-related changes in miRNA in a cartilage. We undertook a microarray study on young and old human cartilages. Findings were validated in an independent cohort. Contrasts between these samples identified twenty differentially expressed miRNAs in a cartilage from old donors, derived from an OA environment which clustered based on OA severity. We identified a number of recognised and novel miRNAs changing in cartilage ageing and OA including miR-126: a potential new candidate with a role in OA pathogenesis. These analyses represent important candidates that have the potential as cartilage ageing and OA biomarkers and therapeutic targets.
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Edward, Deepak P., Hind Alkatan, Qundeel Rafiq, Charles Eberhart, Saleh Al Mesfer, Nicola Ghazi, Leen Al Safieh, Altaf A. Kondkar, and Khaled K. Abu Amero. "MicroRNA Profiling in Intraocular Medulloepitheliomas." PLOS ONE 10, no. 3 (March 25, 2015): e0121706. http://dx.doi.org/10.1371/journal.pone.0121706.
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Corthals, Sophie, Su Ming Sun, Rowan Kuiper, Yvonne de Knegt, Annemiek Broyl, Bronno van der Holt, H. Berna Beverloo, et al. "MicroRNA Profiling In Multiple Myeloma." Blood 116, no. 21 (November 19, 2010): 302. http://dx.doi.org/10.1182/blood.v116.21.302.302.
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Abstract Abstract 302 Background: Multiple Myeloma (MM) is a plasma cell malignancy, characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Prognostic factors in MM include translocations and ISS stage; still, the clinical course is difficult to predict. MicroRNAs (miRNAs) are a class of small non-coding single stranded RNAs involved in posttranscriptional gene regulation, which may be of use in defining MM prognosis and outcome. MiRNAs regulate protein levels by binding to either partially or complete complementary sites in messenger RNAs (mRNAs), leading to translational repression or transcript degradation respectively. In this manner, miRNAs play a role in critical biological processes including cellular growth and differentiation. Specific disease related miRNAs in both acute myeloid leukemia and chronic lymphocytic leukemia have been found with specific miRNA signatures associated with different cytogenetic subtypes. Until now, information available for miRNA expression in MM is limited. Methods: MiRNA expression profiling was performed in 45 newly diagnosed MM patients enrolled in the HOVON-65/GMMG-HD4 trial; a randomized, phase III trial performed to evaluate the efficacy of bortezomib prior to high-dose melphalan (HDM) for response, progression free survival (PFS) and overall survival (OS) in patients with newly diagnosed MM. As controls, four healthy BM samples were obtained from subjects undergoing BM harvest for allogeneic transplantation donorship. For all samples, BM derived CD138 selected plasma cells (PCs) with a minimum purity of > 80% were obtained. RNA was isolated using the miRVANA kit, with subsequent miRNA profiling by TaqMan Human MicroRNA Array v1.0. Unsupervised hierarchical clustering with the centered correlation metric with average linkage was performed using BRB-array tools 3.6.0. For survival analysis, miRNA expression was divided in quartiles: the top quartile vs the rest to identify cases with high expression and the bottom quartile vs the rest for cases with low expression. Log-rank tests for univariate association with PFS and OS were performed for each of the 365 miRNAs using the false discovery rate to correct for multiple testing. Chromosomal abnormalities t(4;14), t(11;14), t(14;16) and deletion 13q14 were determined by FISH analysis. MiRNA expression was compared to mRNA expression, available for 39 out of 45 MM patients, using a Spearman's rank correlation test. mRNA expression was determined by Affymetrix U133 Plus 2.0 arrays (Broyl et al., Blood 2010). Results: Clustering resulted in a dendrogram with 5 clear branches, consisting of 4 MM clusters and 1 normal BM cluster. The MM clusters are characterized by up- and downregulation of distinctive miRNAs: cluster A: upregulation of miRNA clusters miRNA-17∼92 and miRNA-106∼25 (n=23); cluster B: upregulation of miRNA-130a and miRNA-424 (n=8); cluster C: upregulation of miRNA-576 and miRNA-106b (n=9) and cluster D: upregulation of miRNA-372 and miRNA-200a (n=4). An additional cluster of one sample was not defined. MiRNAs predominantly expressed in normal BM were miRNA-28 and miRNA-30c. None of the miRNA clusters correlated with cytogenetic subgroups, i.e. deletion 13q14, t(4;14), t(11;14), and t(14;16) Still, a supervised approach showed significantly higher expression of miRNA-122a, miRNA-33, miRNA-489, miRNA-519e, and miRNA-555 in patients with t(11;14). Upregulation of let-7f, miRNA-194 and miRNA-296 expression were found to be associated with better OS with borderline significance (P = .06). Finally, a significant inverse correlation between miRNA-21 expression and gene expression of two of its validated targets, PDCD4 (P = 2× 10−4) and RECK (P = 8×10−4) was found. PDCD4 is a novel tumor suppressor, whose functions include inhibition of translation through eIF4A/eIF4G. RECK has been shown to be involved in angiogenesis, through inhibition of MMP2 and MMP9. Conclusion: miRNA expression in MM is deregulated compared to normal PCs and MM patients can be classified according to their miRNA expression pattern in four clusters. Furthermore, a trend was found for high expression of miRNAs let-7f, miRNA-194 and miRNA-296 with increased OS. Integration of miRNA and mRNA data shows the putative interaction between miRNA-21 and two of its validated targets; tumor suppressor gene PDCD4 and RECK, suggesting a functional relationship between miRNA expression and development of MM. Disclosures: Sonneveld: Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.
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Yin, James Q., Robert C. Zhao, and Kevin V. Morris. "Profiling microRNA expression with microarrays." Trends in Biotechnology 26, no. 2 (February 2008): 70–76. http://dx.doi.org/10.1016/j.tibtech.2007.11.007.
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Meyer-Rochow, G. Y., D. E. Benn, J. V. Conaglen, D. E. Whittle, M. Kunnimalaiyaan, H. Chen, Q. Y. Duh, et al. "178. Microrna Profiling in Pheochromocytoma." Journal of Surgical Research 151, no. 2 (February 2009): 254. http://dx.doi.org/10.1016/j.jss.2008.11.216.
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Kalluri Sai Shiva, Uma Mahesh, Murali Manohar Kuruva, Sasikala Mitnala, Talukdar Rupjyoti, Rao Guduru Venkat, Spandana Botlagunta, Rajasekhar Kandagaddala, et al. "MicroRNA profiling in periampullary carcinoma." Pancreatology 14, no. 1 (January 2014): 36–47. http://dx.doi.org/10.1016/j.pan.2013.10.003.
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Nair, Nandini, Sandeep Kumar, Sudhip Gupta, and Gregory Dehmer. "MICRORNA PROFILING IN DIASTOLIC DYSFUNCTION." Journal of the American College of Cardiology 57, no. 14 (April 2011): E245. http://dx.doi.org/10.1016/s0735-1097(11)60245-3.
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Pritchard, Colin C., Heather H. Cheng, and Muneesh Tewari. "MicroRNA profiling: approaches and considerations." Nature Reviews Genetics 13, no. 5 (April 18, 2012): 358–69. http://dx.doi.org/10.1038/nrg3198.
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Liu, Chang-Gong, George Adrian Calin, Stefano Volinia, and Carlo M. Croce. "MicroRNA expression profiling using microarrays." Nature Protocols 3, no. 4 (March 13, 2008): 563–78. http://dx.doi.org/10.1038/nprot.2008.14.
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Chugh, Pauline, and Dirk P. Dittmer. "Potential pitfalls in microRNA profiling." Wiley Interdisciplinary Reviews: RNA 3, no. 5 (May 7, 2012): 601–16. http://dx.doi.org/10.1002/wrna.1120.
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Ferretti, Elisabetta, Enrico De Smaele, Agnese Po, Lucia Di Marcotullio, Emanuele Tosi, Maria Salome B. Espinola, Concezio Di Rocco, et al. "MicroRNA profiling in human medulloblastoma." International Journal of Cancer 124, no. 3 (February 1, 2009): 568–77. http://dx.doi.org/10.1002/ijc.23948.
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Kong, William, Jian-Jun Zhao, Lili He, and Jin Q. Cheng. "Strategies for profiling MicroRNA expression." Journal of Cellular Physiology 218, no. 1 (January 2009): 22–25. http://dx.doi.org/10.1002/jcp.21577.
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Dwivedi, Y. "MicroRNA Profiling in Postmortem Brain and Plasma Exosomes: Biomarker Perspective of Suicidality." European Psychiatry 41, S1 (April 2017): S49—S50. http://dx.doi.org/10.1016/j.eurpsy.2017.01.211.
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IntroductionSuicide is a leading cause of death. Although research on the biological aspects of suicide is accumulating, there is no testable biomarker to assess suicidality. miRNAs, small non-coding RNAs, have been implicated in synaptic plasticity, genetic susceptibility to stress and coping to stress response. Because of the presence of microRNAs in circulating body fluids, miRNAs can not only be used as regulators of disease pathologies but also in prognosis and treatment response.ObjectivesWhether miRNAs can be used as biomarker for suicidality.AimsTo examine miRNA expression in brain of suicide victims and in plasma exosomes of suicidal individuals.MethodsmicroRNA expression was studied in prefrontal cortex of depressed suicide subjects and healthy normal controls. Role of microRNAs in synaptic plasticity was studied by examining total and synaptonerosomes. microRNA expression was also studied in plasma exosomes of depressed non-suicide and depressed suicide subjects and healthy normal controls.ResultsWe found a global down–regulation of miRNAs in depressed subjects (21 miRNAs significantly down-regulated). Many of them were synaptically enriched and encoded at nearby chromosomal loci, shared motifs within the 5’-seeds, and shared putative mRNA targets. In addition, we found a dramatic reorganization of microRNAs in a coordinated and cohesive fashion in depressed subjects. We also detected changes in miRNAs in plasma exosomes of depressed suicide subjects that corresponded to microRNA changes in prefrontal cortex.ConclusionOur study provides critical evidence that microRNAs play a major role in suicide pathophysiology and that these microRNAs can be reliably used as peripheral biomarker.Disclosure of interestThe author declares that he has no competing interest.
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Zhu, Hongmei, and Siu-wai Leung. "MicroRNA biomarkers of type 2 diabetes: A protocol for corroborating evidence by computational genomics and meta-analyses." PLOS ONE 16, no. 4 (April 6, 2021): e0247556. http://dx.doi.org/10.1371/journal.pone.0247556.
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Background Few microRNAs were found consistently dysregulated in type 2 diabetes (T2D) that would gain confidence from Big Pharma to develop diagnostic or therapeutic biomarkers. This study aimed to corroborate evidence from eligible microRNAs-T2D association studies according to stringent quality criteria covering both biological and statistical significance in T2D for biomarker development. Methods and analyses Controlled microRNA expression profiling studies on human with T2D will be retrieved from PubMed, ScienceDirect, and Embase for selecting the statistically significant microRNAs according to pre-specified search strategies and inclusion criteria. Multiple meta-analyses with restricted maximum-likelihood estimation and empirical Bayes estimation under the random-effects model will be conducted by metafor package in R. Subgroup and sensitivity analyses further examine the microRNA candidates for their disease specificity, tissue specificity, blood fraction specificity, and statistical robustness of evidence. Biologically relevant microRNAs will then be selected through genomic database corroboration. Their association with T2D is further measured by area under the curve (AUC) of receive operating characteristic (ROC). Meta-analysis of AUC of potential biomarkers will also be conducted. Enrichment analysis on potential microRNA biomarkers and their target genes will be performed by iPathwayGuide and clusterProfiler, respectively. The corresponding reporting guidelines will be used to assess the quality of included studies according to their profiling methods (microarray, RT-PCR, and RNA-Seq). Ethics and dissemination No ethics approval is required since this study does not include identifiable personal patient data. Protocol registration number CRD42017081659.
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Gebauer, Niklas, Christoph Thorns, Veronica Bernard, Andrea Senft, Arne Schillert, Hartmut Merz, Alfred C. Feller, and Heinz-Wolfram Bernd. "MicroRNA Profiling of Low-Grade and Transformed Nodal Marginal Zone Lymphoma Reveals a Similar Signature Pattern Distinct from Diffuse Large B Cell Lymphoma." Acta Haematologica 133, no. 2 (November 4, 2014): 214–20. http://dx.doi.org/10.1159/000363096.
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Background/Aims: As critical post-transcriptional regulators of gene expression, microRNAs are involved in several cellular processes of vital impact including cell growth and apoptosis. Many hematologic malignancies exhibit distinct microRNA signatures. MicroRNA implication in the pathogenesis of nodal marginal zone lymphoma (NMZL), however, remains widely elusive. Methods: Comprehensive morphologic, immunophenotypic and cytogenetic studies were carried out on a cohort of NMZL (n = 30) incorporating indolent as well as transformed MZL. In addition, microRNA signatures were generated, employing a quantitative real-time polymerase chain reaction approach. These were then compared to signatures from cases of diffuse large B cell lymphoma (DLBCL) alongside reactive lymph node controls. Results: While microRNA signatures of low-grade and transformed NMZL did not differ significantly, several microRNAs were differentially expressed between transformed NMZL and DLBCL, hinting at molecularly distinct mechanisms of lymphomagenesis and indicating the biological disparity of transformed NMZL from DLBCL. Conclusion: In the light of the unresolved issue regarding the classification of marginal zone-derived transformed B-cell neoplasms, microRNAs may be a valuable aid in discriminating NMZL from DLBCL. © 2014 S. Karger AG, Basel
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Zhang, Jenny, Dereje D. Jima, Cassandra Jacobs, Randy Fischer, Eva Gottwein, Grace Huang, Patricia L. Lugar, et al. "Patterns of microRNA expression characterize stages of human B-cell differentiation." Blood 113, no. 19 (May 7, 2009): 4586–94. http://dx.doi.org/10.1182/blood-2008-09-178186.
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Abstract Mature B-cell differentiation provides an important mechanism for the acquisition of adaptive immunity. Malignancies derived from mature B cells constitute the majority of leukemias and lymphomas. These malignancies often maintain the characteristics of the normal B cells that they are derived from, a feature that is frequently used in their diagnosis. The role of microRNAs in mature B cells is largely unknown. Through concomitant microRNA and mRNA profiling, we demonstrate a potential regulatory role for microRNAs at every stage of the mature B-cell differentiation process. In addition, we have experimentally identified a direct role for the microRNA regulation of key transcription factors in B-cell differentiation: LMO2 and PRDM1 (Blimp1). We also profiled the microRNA of B-cell tumors derived from diffuse large B-cell lymphoma, Burkitt lymphoma, and chronic lymphocytic leukemia. We found that, in contrast to many other malignancies, common B-cell malignancies do not down-regulate microRNA expression. Although these tumors could be distinguished from each other with use of microRNA expression, each tumor type maintained the expression of the lineage-specific microRNAs. Expression of these lineage-specific microRNAs could correctly predict the lineage of B-cell malignancies in more than 95% of the cases. Thus, our data demonstrate that microRNAs may be important in maintaining the mature B-cell phenotype in normal and malignant B cells.
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Hromadnikova, Ilona, Lenka Dvorakova, Katerina Kotlabova, and Ladislav Krofta. "The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs." International Journal of Molecular Sciences 20, no. 12 (June 18, 2019): 2972. http://dx.doi.org/10.3390/ijms20122972.
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The aim of the study was to verify if quantification of placental specific C19MC microRNAs in plasma exosomes would be able to differentiate during the early stages of gestation between patients subsequently developing pregnancy-related complications and women with the normal course of gestation and if this differentiation would lead to the improvement of the diagnostical potential. The retrospective study on singleton Caucasian pregnancies was performed within 6/2011-2/2019. The case control study, nested in a cohort, involved women that later developed GH (n = 57), PE (n = 43), FGR (n = 63), and 102 controls. Maternal plasma exosome profiling was performed with the selection of C19MC microRNAs with diagnostical potential only (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) using real-time RT-PCR. The down-regulation of miR-517-5p, miR-520a-5p, and miR-525-5p was observed in patients with later occurrence of GH and PE. Maternal plasma exosomal profiling of selected C19MC microRNAs also revealed a novel down-regulated biomarker during the first trimester of gestation (miR-520a-5p) for women destinated to develop FGR. First trimester circulating plasma exosomes possess the identical C19MC microRNA expression profile as placental tissues derived from patients with GH, PE and FGR after labor. The predictive accuracy of first trimester C19MC microRNA screening (miR-517-5p, miR-520a-5p, and miR-525-5p) for the diagnosis of GH and PE was significantly higher in the case of expression profiling of maternal plasma exosomes compared to expression profiling of the whole maternal plasma samples.
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Cioce, Mario, Daniela Rutigliano, Annamaria Puglielli, and Vito Michele Fazio. "Butein-instigated miR-186-5p-dependent modulation of TWIST1 affects resistance to cisplatin and bioenergetics of Malignant Pleural Mesothelioma cells." Cancer Drug Resistance 5, no. 3 (2022): 814–28. http://dx.doi.org/10.20517/cdr.2022.56.
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Aim: Malignant pleural mesothelioma is a chemoresistant tumor, and biphasic and sarcomatoid histologies portend the worst prognosis for malignant pleural mesothelioma (MPM) patients. We obtained the microRNA expression profile of three biphasic-sarcomatoid MPM cell lines to identify commonly expressed microRNAs and evaluate the effect of butein, a chemo-sensitizing compound, on this microRNA subset. Methods: Nanostring-based microRNA profiling and analysis through the ROSALIND platform were employed to identify the commonly modulated microRNAs and their targets. MicroRNA-mimic transfection, Luciferase assay, and Western blotting were employed to show specific perturbation of TWIST1 levels by miR-186-5p. Sphere-forming assays, invasion assay, and metabolic profiling were used to assess the biological consequences of the butein-instigated miR-186-5p-mediated perturbation of TWIST1 levels. TGCA analysis was used to search for the correlation between TWIST1 and miR-186-5p levels in biphasic and epithelioid MPM specimens. Results: We identified a set of perturbed microRNAs, common to three biphasic/sarcomatoid MPM cell lines, after butein treatment. When focusing on miR-186-5p, we unraveled a butein-ignited and miR-186-5p-mediated modulation of TWIST1 levels which affected the 3D anchorage-independent growth, cisplatin resistance, invasion, and bioenergetics of the MPM cell lines tested. We showed that miR-186-5p and TWIST1 levels are anti-correlated in biphasic MPM specimens from TCGA. Conclusion: We unraveled a novel mechanism of action of butein, which attenuated the pro-tumorigenic features of MPM at least through a miR-186-5p-TWIST1 axis. We suggest that those activities converge into the chemo-sensitizing effect of this compound and may be of translational relevance.
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Kulcenty, Katarzyna, Joanna P. Wroblewska, Marcin Rucinski, Emilia Kozlowska, Karol Jopek, and Wiktoria M. Suchorska. "MicroRNA Profiling During Neural Differentiation of Induced Pluripotent Stem Cells." International Journal of Molecular Sciences 20, no. 15 (July 26, 2019): 3651. http://dx.doi.org/10.3390/ijms20153651.
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MicroRNAs (miRNA) play an essential role in the regulation of gene expression and influence signaling networks responsible for several cellular processes like differentiation of pluripotent stem cells. Despite several studies on the neurogenesis process, no global analysis of microRNA expression during differentiation of induced pluripotent stem cells (iPSC) to neuronal stem cells (NSC) has been done. Therefore, we compared the profile of microRNA expression in iPSC lines and in NSC lines derived from them, using microarray-based analysis. Two different protocols for NSC formation were used: Direct and two-step via neural rosette formation. We confirmed the new associations of previously described miRNAs in regulation of NSC differentiation from iPSC. We discovered upregulation of miR-10 family, miR-30 family and miR-9 family and downregulation of miR-302 and miR-515 family expression. Moreover, we showed that miR-10 family play a crucial role in the negative regulation of genes expression belonging to signaling pathways involved in neural differentiation: WNT signaling pathway, focal adhesion, and signaling pathways regulating pluripotency of stem cells.
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Roccaro, Aldo M., Antonio Sacco, Brian Thompson, Xavier Leleu, Abdel Kareem Azab, Feda Azab, Judith Runnels, et al. "MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma." Blood 113, no. 26 (June 25, 2009): 6669–80. http://dx.doi.org/10.1182/blood-2009-01-198408.
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Abstract Detailed genomic studies have shown that cytogenetic abnormalities contribute to multiple myeloma (MM) pathogenesis and disease progression. Nevertheless, little is known about the characteristics of MM at the epigenetic level and specifically how microRNAs regulate MM progression in the context of the bone marrow milieu. Therefore, we performed microRNA expression profiling of bone marrow derived CD138+ MM cells versus their normal cellular counterparts and validated data by qRT-PCR. We identified a MM-specific microRNA signature characterized by down-expression of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/-181a/-181b (P < .01). We investigated the functional role of microRNA-15a and -16 and showed that they regulate proliferation and growth of MM cells in vitro and in vivo by inhibiting AKT serine/threonine-protein-kinase (AKT3), ribosomal-protein-S6, MAP-kinases, and NF-κB-activator MAP3KIP3. Moreover, miRNA-15a and -16 exerted their anti-MM activity even in the context of the bone marrow milieu in vitro and in vivo. These data indicate that microRNAs play a pivotal role in the biology of MM and represent important targets for novel therapies in MM.
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Palma, Catalina A., Elise Tonna, Adam J. Bryant, Vivek Jayaswal, David Agapiou, Yee Hwa Yang, David Ma, and Mark Lutherborrow. "MicroRNA Expression in Acute Myeloid Leukaemia and Their Effects on the Differentiation of Acute Myeloid Leukaemia Cells." Blood 118, no. 21 (November 18, 2011): 2430. http://dx.doi.org/10.1182/blood.v118.21.2430.2430.
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Abstract Abstract 2430 Acute myeloid leukaemia (AML) is typified by an aberrant halt in maturation of myeloid progenitor cells, leading to uncontrolled proliferation of immature blasts. In the majority of cases of AML with normal karyotype, the underlying cause of the maturation arrest remains unclear. MicroRNAs, small inhibitory RNAs, are known to be dysregulated in cancers and have been postulated to play a causative role in leukaemogenesis. We aimed to investigate the contribution of aberrant microRNA expression to the inhibition of maturation in AML cells. MicroRNA expression profiling was performed on the bone marrow of 28 AML patients with normal karyotype and 8 normal controls. Differential expression was confirmed by qRT-PCR. We found that the expression of a panel of 12 microRNAs was able to accurately separate AML-M1 and AML-M5 subtypes. The AML-M1 subtype represents a more immature cell population when compared to the monoblast morphology observed in AML-M5. Four candidate microRNAs, miR-181a, -146a, -130a and -135b were selected for further investigation based in their putative targeting of key monocytic transcription factors as determined by in silico modelling followed by luciferase assays. In vitro monocyte and macrophage differentiation of HL60 and NB4 cell lines with 1,25-dihydroxyvitamin D3 and/or phorbol-12-myristate-13-acetate treatment resulted in a significant decrease in all four candidate microRNAs (measured by qRT-PCR), supporting the hypothesis that candidate microRNA over-expression in AML-M1 may contribute to its maturation arrest. Over-expression of the candidate microRNAs by transfection with Pre-miR microRNA precursor molecules (Ambion) into the HL60 and NB4 monocyte differentiation model, resulted in the significant suppression of CD14 (Figure, *p <0.05 compared to Scrambled control) and CD15 expression, markers of monocytes and granulocytes respectively. Conversely, knockdown of miR-181a, -146a, -130a and -135b with miRCURY LNA microRNA knockdown probes (Exiqon) induced an increase in CD14 expression in HL60 cells compared to non-targeting Scrambled control. An important regulatory role of these microRNAs in myeloid/monocytic differentiation is strongly suggested by their targeted suppression of the key transcription factors KLF4, MAFB, IRF8, HOXA10, MCL1 and PU.1 which was confirmed by luciferase reporter assay. This study provides evidence that the over-expressed microRNAs discovered in our profiling work between AML-M1 and AML-M5 are biologically relevant microRNAs, which have the potential to affect the maturation potential of AML cells. Disclosures: No relevant conflicts of interest to declare.
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Nam, Eun Ji, Ga Won Yim, Jae Hoon Kim, Sunghoon Kim, Sang Wun Kim, Jae-Wook Kim, and Young-Tae Kim. "Relationship of microRNA expression profiles and recurrence in advanced serous ovarian carcinoma." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 5557. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5557.
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5557 Background: Most patients with epithelial ovarian cancer eventually succumb to chemo-resistant disease. Although microRNAs have been recognized as important regulators of gene expression, little is known about microRNA expression profiles in recurrent serous ovarian carcinoma. We assessed the microRNA expression profiles which contribute to recurrence in advanced serous ovarian carcinoma. Methods: Eight pairs of primary and recurrent tumor samples from 8 patients with advanced serous ovarian carcinoma and 4 normal ovarian samples from patients treated for benign uterine disease between May 2006 and Dec 2012 were examined using miRNA microarray. microRNA profiling were validated using real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: Alterations of microRNA expression profiles in primary and recurrent tumor samples have similar patterns when compared with normal ovarian tissues. Among 31 up-regulated microRNAs more than 4-fold in primary tumors, 27 microRNAs were also significantly up-regulated in recurrent tumor samples. Likewise, Among 35 down-regulated microRNAs more than 4-fold in primary tumors, 34 microRNAs were also significantly down-regulated in recurrent tumor samples. Comparing to primary tumor, we found 60 microRNAs which were significantly up-regulated, including miR-630, 370, and 575, and 52 microRNAs which were significantly down-regulated, including miR-509-3p, 514a-3p, and 506-3p in recurrent serous ovarian carcinoma. Conclusions: Our results indicate that dysregulation of microRNAs may play a role in recurrence of serous ovarian carcinoma.
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de Leeuw, David C., Willemijn de van den Ancker, Fedor Denkers, Renee X. de Menezes, Theresia M. Westers, Gert J. Ossenkoppele, Arjan A. Van de Loosdrecht, and Linda Smit. "Microrna Profiling Classifies Acute Leukemias of Ambiguous Lineage As Either Acute Myeloid Leukemia or Acute Lymphoid Leukemia." Blood 120, no. 21 (November 16, 2012): 1443. http://dx.doi.org/10.1182/blood.v120.21.1443.1443.
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Abstract Abstract 1443 Introduction Classification of acute leukemia (AL) is based on commitment of the leukemic cells to either the myeloid or the lymphoid lineage. However, a small percentage of AL cases lacks immunophenotypical lineage commitment or displays features of both hematopoietic lineages. These leukemias of ambiguous lineage represent a heterogeneous category of AL that cannot be classified as either myeloid AL (AML) or lymphoid AL (ALL). This presents a major hurdle for choice of treatment, because it is unsettled whether these patients benefit from AML or ALL treatment regimens or a mixture of both. Better diagnostic tools to define the lineage of origin for these AL would be instrumental to direct therapy decision making. MicroRNAs are small single stranded RNA molecules which regulate gene expression by promoting degradation of mRNAs or repressing their translation. MicroRNA expression profiles have been shown to accurately discriminate AL of the lymphoid lineage from AL of the myeloid lineage. Here, we investigated microRNA expression profiles of leukemias of ambiguous lineage to classify them as either AML or ALL. Methods MicroRNA expression profiles of nine patients with leukemia of ambiguous lineage and eleven patients with AML, B-ALL or T-ALL were analyzed using microarray analysis. MicroRNAs differentially expressed between the myeloid and lymphoid lineage were selected using Linear Model for Microarray Analysis (LIMMA) and used for unsupervised clustering of the ambiguous lineage leukemias with the AML, B-ALL and T-ALL samples. The top five most discriminating microRNAs were selected for qRT-PCR validation in eight additional ambiguous lineage cases, five AML or ALL cases and two control cell lines. Results Unsupervised clustering analysis of the AML, B-ALL and T-ALL samples resulted in a clear separation between the myeloid and lymphoid lineages. Top differentially expressed microRNAs were miR-199b, miR-27a/b, miR-223, miR-23a, miR-221 and miR-150. When comparing leukemias of ambiguous lineage with AML, B-ALL and T-ALL using LIMMA, no clear differences were found, indicating that leukemias of ambiguous lineage are not a separate entity. Moreover, unsupervised clustering of all AL samples using the top 10 percent of most variable microRNAs resulted in clustering of leukemias of ambiguous lineage with either AML, B-ALL or T-ALL and showed comparable expression profiles. Expression analysis by qRT-PCR of the five most discriminative microRNAs on the additional samples, including leukemias of ambiguous lineage, was able to accurately assign these leukemias to the lineage of origin. Conclusion MicroRNA expression profiling of leukemias of ambiguous lineage indicated the presence of a myeloid or lymphoid lineage-specific genotype despite an indistinct immunophenotype. Analyzing microRNA expression at diagnosis to classify acute leukemias of ambiguous lineage as either AML or ALL might be instrumental to therapeutic decision making. Disclosures: No relevant conflicts of interest to declare.
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Haapa-Paananen, S., P. Chen, S. Hautaniemi, P. Kohonen, M. Peräla, and O. Kallioniemi. "589 Precursor MicroRNA Functional Profiling Identifies MicroRNAs Essential for Glioblastoma Proliferation." European Journal of Cancer 48 (July 2012): S140. http://dx.doi.org/10.1016/s0959-8049(12)71246-7.
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Choi, Ji-Woong, Sung-Min Kang, Youngkyun Lee, Su-Hyung Hong, Nicholas A. Sanek, W. Scott Young, and Heon-Jin Lee. "MicroRNA profiling in the mouse hypothalamus reveals oxytocin-regulating microRNA." Journal of Neurochemistry 126, no. 3 (June 11, 2013): 331–37. http://dx.doi.org/10.1111/jnc.12308.
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Gunawardena, I., J. Fitzgerald, A. Morley, D. J. Hussey, C. M. Woods, and A. S. Carney. "Micro-ribonucleic acids in head and neck cancer: an introduction." Journal of Laryngology & Otology 127, S2 (April 24, 2013): S2—S7. http://dx.doi.org/10.1017/s0022215113000753.
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AbstractBackground and methods:Head and neck cancer is the sixth most common cancer worldwide. Advances in management have not greatly altered overall survival. Over the last decade, there have been significant scientific advances in our knowledge of cell cycle regulation and the complex oncogenic processes. MicroRNAs are small, non-coding RNAs which are integral to the regulation of gene expression and which play a part in carcinogenesis. The literature on the role of microRNA in head and neck cancer is reviewed.Objective:To introduce the role and significance of microRNAs in head and neck cancer.Results:The possibilities of incorporating microRNAs into clinical practice are discussed, including their potential role in diagnosis, prognosis, prediction of metastatic spread, therapy and tumour surveillance.Conclusion:Discoveries in expression profiling of microRNA in head and neck oncology promise advancements in the diagnosis, prognosis and therapy of these cancers.