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1

Shao, Liying, Ranran Wang, Yunxiao Sun, et al. "Delivery of MicroRNA-let-7c-5p by Biodegradable Silica Nanoparticles Suppresses Human Cervical Carcinoma Cell Proliferation and Migration." Journal of Biomedical Nanotechnology 16, no. 11 (2020): 1600–1611. http://dx.doi.org/10.1166/jbn.2020.2989.

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Human cervical cancer is the most common gynecological malignancy. The continuous development of nanotechnology has allowed the wide use of nanomaterials in cancer treatment. Nanoparticles can be used as gene carriers because of their surface effect and small-size effect. MicroRNA-let-7c-5p (miR-let-7c-5p) belongs to the let-7 family. Although it has been reported to exert a tumor suppressive effect in a variety of cancers, the exact role and mechanism of miR-let-7c-5p in the progression of cervical cancer are unclear. In this study, we synthesized flower-shaped SiO2 –PEI nanoparticles with high pDNA/siRNA loading rates. This nanoparticle with miR-let-7c-5p-expressed plasmid could effectively transfer miR-let-7c-5p to human epithelial carcinoma (HeLa) cells. In addition, the combination of nanomaterials and gene therapy could inhibit the development of cancer under the conditions of extremely low cytotoxicity. These findings provided a new anticancer strategy based on F-SiO2 -polyethyleneimine/miR-let-7c-5p (FSP-let-7c-5p)nanoparticles and indicated that miR-let-7c-5p/IGF-1R/PI3K/AKT and β-catenin/SLUG could be used as new potential targets for the treatment of cervical cancer.
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2

Zhou, Zihui, Yuanshan Lu, Yao Wang, Lin Du, Yunpeng Zhang, and Jie Tao. "Let-7c regulates proliferation and osteodifferentiation of human adipose-derived mesenchymal stem cells under oxidative stress by targeting SCD-1." American Journal of Physiology-Cell Physiology 316, no. 1 (2019): C57—C69. http://dx.doi.org/10.1152/ajpcell.00211.2018.

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Osteoporosis is a progressive bone disease characterized by decreased bone mass and density, which usually parallels a reduced antioxidative capacity and increased reactive oxygen species formation. Adipose-derived mesenchymal stem cells (ADMSCs), a population of self-renewing multipotent cells, are a well-recognized source of potential bone precursors with significant clinical potential for tissue regeneration. We previously showed that overexpressing stearoyl-CoA desaturase 1 (SCD-1) promotes osteogenic differentiation of mesenchymal stem cells. Micro-RNAs (miRNAs) are noncoding RNAs recently recognized to play key roles in many developmental processes, and miRNA let-7c is downregulated during osteoinduction. We found that let-7c was upregulated in the serum of patients with postmenopausal osteoporosis compared with healthy controls. Levels of let-7c during osteogenic differentiation of ADMSCs were examined under oxidative stress in vitro and found to be upregulated. Overexpression of let-7c inhibited osteogenic differentiation, whereas inhibition of let-7c function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase activity, and matrix mineralization. The luciferase reporter assay was used to validate SCD-1 as a target of let-7c. Further experiments showed that silencing of SCD-1 significantly attenuated the effect of let-7c inhibitor on osteoblast markers, providing strong evidence that let-7c modulates osteogenic differentiation by targeting SCD-1. Inhibition of let-7c promoted the translocation of β-catenin into nuclei, thus activating Wnt/β-catenin signaling. Collectively, these data suggest that let-7c is induced under oxidative stress conditions and in osteoporosis, reducing SCD-1 protein levels, switching off Wnt/β-catenin signaling, and inhibiting osteogenic differentiation. Thus, let-7c may be a potential therapeutic target in the treatment of osteoporosis and especially postmenopausal osteoporosis.
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3

Narumanchi, Suneeta, Karri Kalervo, Sanni Perttunen, et al. "Inhibition of let-7c Regulates Cardiac Regeneration after Cryoinjury in Adult Zebrafish." Journal of Cardiovascular Development and Disease 6, no. 2 (2019): 16. http://dx.doi.org/10.3390/jcdd6020016.

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The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.
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4

Li, Ting, Yanhong Huang, Wenkai Zhou, and Qichang Yan. "Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells." BioMed Research International 2020 (March 16, 2020): 1–9. http://dx.doi.org/10.1155/2020/6069390.

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Background. Oxidative stress is an important factor during age-related cataract formation. Apoptosis and autophagy induced by oxidative stress have been reported as key factors in age-related cataract. In our research, we investigated the role of let-7c-3p in the regulation of autophagy and apoptosis during the formation of age-related cataract. Material and Methods. Real-time PCR and western blot were employed to detect the expression of let-7c-3p in the tissues of age-related cataract. Human lens epithelial cells (LECs) were treated with H2O2 as an age-related cataract model. The extent of apoptosis was measured by flow cytometry and western blot. To detect autophagy, immunofluorescence was used to analyze the spot number of LC3, and western blot was used to detect the expression of LC3-II/I and ATG3. The molecular mechanisms of let-7c-3p regulating autophagy via ATG3 under oxidative stress were performed by a luciferase report gene assay and rescue experiment. Results. Downregulation of let-7c-3p was found in the age-related cataract group aged >65 years relative to the age-related cataract group aged ≤65 years. Consistently, the expression of let-7c-3p was also lower under oxidative stress. The activities of LEC apoptosis and autophagy induced by oxidative stress were inhibited by let-7c-3p. By the bioinformatics database and the luciferase reporter assay, ATG3 was found to be a direct target of let-7c-3p. Let-7c-3p reduced the ATG3-mediated autophagy level, which was induced by oxidative stress in LECs. Conclusion. Let-7c-3p inhibits autophagy by targeting ATG3 in LECs in age-related cataract.
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5

Wang, Zhenguo, Cuixing Zhou, Yangyang Sun, Yimeng Chen та Dong Xue. "Let-7c-5p Is Involved in Chronic Kidney Disease by Targeting TGF-β Signaling". BioMed Research International 2020 (13 червня 2020): 1–8. http://dx.doi.org/10.1155/2020/6960941.

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The purpose of the present study was to investigate the expressions of hsa-let-7c-5p and TGF-β signaling-related molecules and their correlations with clinical characteristics in chronic kidney disease (CKD). Twenty-three biopsy specimens of CKD patients and 20 negative control tissues were selected. Quantitative real-time PCR (qPCR) was used for the detection of hsa-let-7c-5p, transforming growth factor β (TGF-β) and TGF-β receptor type 1 (TGF-βR1) expression levels. Target gene of hsa-let-7c-5p was verified by dual-luciferase reporter assay. A significant decrease of hsa-let-7c-5p expression in CKD tissue was found, compared with that of normal renal tissues (p<0.01). Expression levels of TGF-β in CKD were increased, compared with that of normal kidney tissue (p<0.001). The difference in the expression of TGF-β R1 between CKD tissues and normal renal tissues was not significant (p>0.05). A negative correlation was found between the expression of TGF-β and renal tissue hsa-let-7c-5p levels. Furthermore, hsa-let-7c-5p was identified to regulate TGF- β1 by directly binding with the 167-173 site in the 3′ untranslated region. Decreased hsa-let-7c-5p levels in CKD patients was found to be associated with disease severity, which shows a negative correlation with proteinuria and creatinine levels, and a positive correlation with estimated glomerular filtration rate (eGFR), while relative TGF-β1 expression had a positive correlation with creatinine level. In summary, changes in hsa-let-7c-5p expression and its target gene TGF-β are associated with the disease status of CKD. Let-7c-5p may contribute to the pathogenesis of renal fibrosis through TGF-β signaling, a potential diagnostic and therapeutic target of the disease.
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6

Shah, Yatrik M., Keiichirou Morimura, Qian Yang, Tomotaka Tanabe, Mitsuhiro Takagi та Frank J. Gonzalez. "Peroxisome Proliferator-Activated Receptor α Regulates a MicroRNA-Mediated Signaling Cascade Responsible for Hepatocellular Proliferation". Molecular and Cellular Biology 27, № 12 (2007): 4238–47. http://dx.doi.org/10.1128/mcb.00317-07.

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ABSTRACT Activation of peroxisome proliferator-activated receptor α (PPARα) leads to hepatocellular proliferation and liver carcinomas. The early events mediating these effects are unknown. A novel mechanism by which PPARα regulates gene expression and hepatocellular proliferation was uncovered. MicroRNA (miRNA) expression profiling demonstrated that activated PPARα was a major regulator of hepatic miRNA expression. Of particular interest, let-7C, an miRNA important in cell growth, was inhibited following 4-h treatment and 2-week and 11-month sustained treatment with the potent PPARα agonist Wy-14,643 in wild-type mice. let-7C was shown to target c-myc via direct interaction with the 3′ untranslated region of c-myc. The PPARα-mediated induction of c-myc via let-7C subsequently increased expression of the oncogenic mir-17-92 cluster; these events did not occur in Pparα-null mice. Overexpression of let-7C decreased c-myc and mir-17 and suppressed the growth of Hepa-1 cells. Furthermore, using the human PPARα-expressing mouse model, which is responsive to Wy-14,643 effects on β-oxidation and serum triglycerides but resistant to hepatocellular proliferation and tumorigenesis, we demonstrated a critical role for let-7C in liver oncogenesis. Wy-14,643 treatment did not inhibit let-7C or induce c-myc and mir-17 expression. These observations reveal a let-7C signaling cascade critical for PPARα agonist-induced liver proliferation and tumorigenesis.
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7

Zergani, Emel, Amir Rashidi, Jalal Rostamzadeh, Jens Tetens, and Mohammad Razmkabir. "Effect of a Novel Variant with Let-7c MicroRNA Gene on Litter Size in Markhoz Goats." Ruminants 2, no. 4 (2022): 471–77. http://dx.doi.org/10.3390/ruminants2040033.

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This study was focused on identifying the effects of single nucleotide polymorphisms (SNPs) located on an entire region of the let-7c miRNA gene with consideration of its ability to promote litter size in Markhoz goats. The Markhoz goat, the native breed in Iran, is important for its reproductive traits, such as litter size. DNA polymorphism of let-7c miRNA gene was revealed and considered for further studies for its effect on litter size in Markhoz goats. PCR-SSCP analysis investigated different band patterns for this miRNA; however, sequencing results have detected only an A to T substitution located five nucleotides downstream of the let-7c miRNA gene. The chi-squared test showed that the let-7c miRNA gene locus was out of the Hardy–Weinberg equilibrium (HWE) and has significant effect (p < 0.05). Furthermore, the least-square analysis indicated that the let-7c miRNA gene does not affect prolificacy in the Markhoz goat (p > 0.05). In sum, all loci failed to have a significant effect on the litter size trait (p > 0.05). Moreover, years of kidding and parity had no significant impact on let-7c_S (p > 0.05); however, the let-7c_B affected the litter size trait significantly (p < 0.05). Additionally, binary logistic regression and chi-square analysis revealed that allele A of the detected SNP within 3′ UTR region of the let-7c gene had a non-significant effect on litter size in the studied goats (p > 0.05).
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8

Wang, Lan, Jing Zou, and Jing Zhang. "Dysregulation of let-7c-5p/Tyrosyl-DNA phosphodiesterase 1 axis indicates an unfavorable outcome in gastric cancer." European Journal of Inflammation 20 (January 2022): 205873922110692. http://dx.doi.org/10.1177/20587392211069258.

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Introduction Tyrosyl-DNA phosphodiesterase 1 (TDP1) can repair oxidative damage-caused 3′-phosphoglycolates and promote cancer progression. However, the clinical significance of TDP1 and its correlation with microRNAs (miRNAs) in gastric cancer (GC) remains unknown. Methods The relationship of TDP1 or let-7c-5p with the clinical outcomes of GC was determined by a tissue microarray and TCGA dataset. Cell viability and invasion were assessed by MTT and Transwell assays. Pearson correlation analysis, luciferase gene report, qRT-PCR, and Western blot analyses were used to analyze the interaction between TDP1 and let-7c-5p in GC tissues and cells. Results We found that TDP1 expression was elevated in GC tissues and associated with the dysregulation of let-7c-5p. Knockdown of TDP1 inhibited GC cell proliferation and invasion. let-7c-5p could be found to bind with TDP1, reduce its expression levels, and represent a predictive marker in GC. Conclusion Our findings demonstrated that dysregulation of let-7c-5p/TDP1 axis could predict a poor prognosis in GC.
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9

Fan, James, Joanna Gemel, Eric C. Beyer, and Gabrielle Lapping-Carr. "Plasma Levels of MicroRNA Let-7c-5p May Predict Risk of Acute Chest Syndrome in Patients with Sickle Cell Disease." International Journal of Molecular Sciences 26, no. 8 (2025): 3831. https://doi.org/10.3390/ijms26083831.

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Acute chest syndrome (ACS) is among the most serious complications of sickle cell disease (SCD). While the pathogenesis of ACS is incompletely understood, endothelial damage and microvascular occlusion are critical components. Our previous studies have implicated small extracellular vesicles in the plasma of subjects with SCD in causing endothelial dysfunction. This suggested that microRNAs within these small EVs might be responsible for endothelial damage. The sequencing of microRNAs in small EVs from the plasma of subjects with SCD revealed that several miRNAs were differentially expressed between subjects with and without ACS history, including let-7c-5p. In a replication cohort, plasma let-7c-5p levels were quantified via RT-qPCR. The baseline plasma let-7c-5p level was twofold higher in patients without previous ACS. Furthermore, we observed a positive correlation between let-7c-5p levels and time to subsequent ACS events. These findings suggest a role for let-7c-5p in endothelial disruption underlying ACS pathogenesis. It may also serve as a novel biomarker for ACS detection and the prediction of disease progression.
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10

Zhang, Hang-Hu, Cai-Xue Li, and Lan-Fang Tang. "The Differential Expression Profiles of miRNA-let 7a, 7b, and 7c in Bronchoalveolar Lavage Fluid From Infants With Asthma and Airway Foreign Bodies." Journal of Evidence-Based Integrative Medicine 24 (January 1, 2019): 2515690X1882190. http://dx.doi.org/10.1177/2515690x18821906.

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The aim of this study was to investigate the expression patterns of miRNA-let 7a, 7b, and 7c in bronchoalveolar lavage fluid in infants with asthma and airway foreign bodies. Between January 2016 and February 2017, 27 infants were included and divided into observation group (infants with asthma, n = 15) and control group (infants with airway foreign bodies, n = 12). The differential expression profiles of miRNA-let 7a, 7b, and 7c were determined by reverse transcription–polymerase chain reaction in bronchoalveolar lavage fluid (BALF) from infants of the 2 groups. The BALF was collected from infants undergoing flexible bronchoscopy. MiRNA-let 7a, 7b, and 7c increased significantly in infants from observation group as compared with control group (2.72 ± 0.48 vs 1, 8.23 ± 1.64 vs 1, 3.16 ± 0.62 vs 1, respectively). The increased expression of miRNA-let 7a, 7b, and 7c were associated with the asthma of infants.
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11

Kalantzakos, Thomas J., Luke E. Sebel, James Trussler, et al. "MicroRNA Associated with the Invasive Phenotype in Clear Cell Renal Cell Carcinoma: Let-7c-5p Inhibits Proliferation, Migration, and Invasion by Targeting Insulin-like Growth Factor 1 Receptor." Biomedicines 10, no. 10 (2022): 2425. http://dx.doi.org/10.3390/biomedicines10102425.

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Differential microRNA (miRNA) expression can portend clear cell renal cell carcinoma (ccRCC) progression. In a previous study, we identified a subset of dysregulated miRNA in small renal masses, pT1 ccRCC (≤5 cm) that are associated with an aggressive phenotype. The present study investigated miRNA expression in clinical stage I (cT1) tumors (≤5 cm), comparing pathologic stage I (pT1) tumors to those upstaged to pathologic stage 3 (pT3) after surgery following identification of renal vein invasion or invasion into adjacent fat tissue within Gerota’s fascia. Twenty cT1 tumors were examined in an miRNA screening, 10 pT1 and 10 pT3 tumors. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of let-7c-5p and its protein target insulin-like growth factor 1 receptor (IGF1R). Cells were transfected with pre-let-7c-5p and assessed through cell proliferation, migration, and invasion assays. IGF1R expression was evaluated through Simple Western, and interaction between let-7c-5p and IGF1R was confirmed via luciferase reporter assay. Screening identified 20 miRNA, including let-7c-5p, that were dysregulated between pT1 and pT3 upstaged tumors. This miRNA was also downregulated in our previous study of pT1 tumors that progressed to metastatic disease. Transfection of ccRCC cells with pre-let-7c-5p significantly inhibited proliferation, migration, invasion, and IGF1R expression. These findings suggest that miRNA dysregulation is involved in ccRCC progression, specifically through invasion, and that let-7c-5p downregulation contributes to the aggressiveness of small ccRCC tumors, in part, through its regulation of IGF1R.
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12

Banerjee, Sami, Na Xie, Huachun Cui, et al. "MicroRNA let-7c Regulates Macrophage Polarization." Journal of Immunology 190, no. 12 (2013): 6542–49. http://dx.doi.org/10.4049/jimmunol.1202496.

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13

Fan, James, Joanna Gemel, Theodore Lang, Eric Beyer, and Gabrielle Lapping-Carr. "433 Is miR let-7c protective against Acute Chest Syndrome in Sickle Cell Disease?" Journal of Clinical and Translational Science 6, s1 (2022): 84–85. http://dx.doi.org/10.1017/cts.2022.251.

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OBJECTIVES/GOALS: We have shown that small extracellular vesicles (exosomes) isolated from patients with a history of ACS disrupt the endothelium in vitro. Sequencing of miRNA contents of these vesicles suggested that miR let-7c was differentially expressed. The current study was designed to determine the relationship between miR let-7c levels and ACS. METHODS/STUDY POPULATION: We identified 16 subjects from the SCD Lungomics biobank at the University of Chicago Comer and La Rabida Childrens Hospitals who had samples obtained at baseline. Among them, 9 had a history of ACS (ACS(+)) and 7 did not (ACS(-)). For all subjects, we reviewed clinical data relevant to their SCD and laboratory data (including hemoglobin, absolute reticulocyte count, white blood cell count) obtained at the same time as the baseline samples. RNA was isolated from the plasma and miR let7c was quantified using quantitative RT-PCR. RESULTS/ANTICIPATED RESULTS: Subjects were similar clinically, except that those with a history of ACS were more likely to be on hydroxyurea (p<0.05) and to have obstructive sleep apnea (p<0.05). Hematologic laboratory values were similar irrespective of ACS history. The mean miR let-7c level was 2-fold less in subjects with a history of ACS than in those who had never had ACS (p<0.05). A plasma miR let-7c level < 1 (normalized to the control subjects) had a positive predictive value of 0.78 for history of ACS and a sensitivity of 78% and specificity of 71%. Among subjects with a history of ACS, the let7c levels did not correlate with time since the last ACS event. However, among subjects who developed ACS following the baseline samples, higher miR let-7c levels correlated with increased length of time to next ACS event (R=0.8). DISCUSSION/SIGNIFICANCE: Our results in a group of subjects with SCD show that plasma miR let-7c levels are decreased in subjects with a history of ACS. They suggest that miR let-7c may be protective against development of ACS and that measurement of its levels could be a useful biomarker to assess or predict risk for this complication of SCD.
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Izzo, Antonella, Rosanna Manco, Tiziana de Cristofaro, et al. "Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the Hearts of Down Syndrome Fetuses." International Journal of Genomics 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/8737649.

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Dosage-dependent upregulation of most of chromosome 21 (Hsa21) genes has been demonstrated in heart tissues of fetuses with Down syndrome (DS). Also miRNAs might play important roles in the cardiac phenotype as they are highly expressed in the heart and regulate cardiac development. Five Hsa21 miRNAs have been well studied in the past: miR-99a-5p, miR-125b-2-5p, let-7c-5p, miR-155-5p, and miR-802-5p but few information is available about their expression in trisomic tissues. In this study, we evaluated the expression of these miRNAs in heart tissues from DS fetuses, showing that miR-99a-5p, miR-155-5p, and let-7c-5p were overexpressed in trisomic hearts. To investigate their role, predicted targets were obtained from different databases and cross-validated using the gene expression profiling dataset we previously generated for fetal hearts. Eighty-five targets of let-7c-5p, 33 of miR-155-5p, and 10 of miR-99a-5p were expressed in fetal heart and downregulated in trisomic hearts. As nuclear encoded mitochondrial genes were found downregulated in trisomic hearts and mitochondrial dysfunction is a hallmark of DS phenotypes, we put special attention to let-7c-5p and miR-155-5p targets downregulated in DS fetal hearts and involved in mitochondrial function. The let-7c-5p predicted target SLC25A4/ANT1 was identified as a possible candidate for both mitochondrial and cardiac anomalies.
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Ikeda, Kazuhiko, Kayo Harada, Kazuei Ogawa, Philip J. Mason, Monica Bessler, and Yasuchika Takeishi. "Expression of Let-7 Micro RNAs in Transgenic Mice Overexpressing Truncated Hmga2." Blood 120, no. 21 (2012): 3470. http://dx.doi.org/10.1182/blood.v120.21.3470.3470.

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Abstract Abstract 3470 Expression of HMGA2 is negatively regulated by binding of let-7-family micro RNAs (miRNAs) to specific sites in 3' untranslated region (UTR) of HMGA2. Either downregulation of let-7 or truncation of HMGA2 is thought to cause overexpression of HMGA2. Overexpression of HMGA2 mRNA due to truncation of its 3'UTR by chromosomal translocation was reported in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH; Inoue et al, Blood, 2006). Accordingly, we recently established transgenic ΔHmga2 mice with 3'UTR-truncated Hmga2 cDNA, which revealed a clonal growth advantage of hematopoietic cells overexpressing Hmga2 mRNA that may lead to expansion of a PNH cell (Ikeda et al, Blood, 2011). It has also been reported that HMGA2 mRNA is overexpressed whereas let-7b and −7c are downregulated in peripheral blood cells from the majority of patients with PNH (Murakami et al, BJH, 2012). Although downregulation of let-7-family miRNAs may in part explain overexpression of HMGA2 mRNA, not only full-length HMGA2 mRNA but also short transcript variants of HMGA2 mRNA without 3'UTR are overexpressed in most of these patients. Thus, we aimed to investigate the influence of overexpression of 3'UTR-truncated Hmga2 mRNA, which mimics its short transcript variant, on expression of let-7-family miRNAs. We evaluated expression of let-7a, -7b, and -7c miRNAs in bone marrow (BM) and spleen cells of 12 week-old ΔHmga2 mice (n= 3–4) and wild-type (WT) mice (n= 3–4) using quantitative real-time RT-PCR. Relative expression levels of let-7a (mean ± SD, 1.14 ± 0.57 and 1.62 ± 1.05, respectively), -7b (0.76 ± 0.38 and 1.14 ± 0.77), and -7c (0.62 ± 0.47 and 0.96 ± 0.51) of BM cells were not significantly different between WT mice and ΔHmga2 mice. However, relative expression level of let-7c was significantly higher in spleen cells of ΔHmga2 mice (11.75 ± 2.10) compared with WT mice (1.47 ± 1.19; P < .01). Expression of let-7a (2.46 ± 2.72 and 20.20 ± 25.22) and −7b (1.43 ± 1.62 and 5.27 ± 4.05) was not significantly different in spleen between WT mice and ΔHmga2 mice. Relative expression levels of let-7c were higher in spleen cells compared with those in BM cells in ΔHmga2 mice (P < .01). Therefore, differences in cell lineage or differentiation status might alter expression of let-7-family miRNAs and 3'UTR-truncated Hmga2 may further influence let-7 expression in a tissue specific manner. However, the cause of downregulation of let-7b and -7c, and overexpression of 3'UTR truncated variants of HMGA2 in patients with PNH remains to be elucidated. Disclosures: No relevant conflicts of interest to declare.
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Yoshioka, Hiroki, Hanane Horita, Yosuke Tsukiboshi, Hisaka Kurita, Aya Ogata, and Kenichi Ogata. "Cleft Palate Induced by Mycophenolate Mofetil Is Associated with miR-4680-3p and let-7c-5p in Human Palate Cells." Non-Coding RNA 11, no. 1 (2025): 12. https://doi.org/10.3390/ncrna11010012.

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Background/Objectives: Cleft palate is a birth defect associated with environmental and genetic factors. Disturbance of microRNAs (miRNAs) and exposure to medicinal agents during pregnancy can cause cleft palate. Although an association between medicine-induced cleft palate and miRNAs has been suggested, it remains to be fully elucidated. This study aimed to clarify the molecular mechanism underlying mycophenolate mofetil (MPM)-induced inhibition of cell proliferation and miRNA expression in human embryonic palatal mesenchymal (HEPM) cells. Methods: Cell viability, apoptosis, and cell cycle-related markers were evaluated 48 h after MPM treatment. In addition, miRNA levels and expression of their downstream genes were measured, and a rescue experiment was performed using miR-4680-3p and/or let-7c-5p inhibitors. Results: MPM dose-dependently reduced HEPM cell viability. Additionally, MPM treatment suppressed cyclin-D1, cyclin E1, cyclin-dependent kinase (CDK)-2, and CDK6 expression in HEPM cells. Furthermore, MPM upregulated miR-4680-3p and let-7c-5p expression and downregulated the downstream genes of each miRNA. Moreover, miR-4680-3p and/or let-7c-5p inhibitors alleviated MPM-induced inhibition of cell proliferation. Conclusions: These results suggest that MPM-induced cleft palate is associated with miR-4680-3p and let-7c-5p expression in HEPM cells.
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Fiala, Ondřej, Ondřej Šorejs, Petr Hošek, et al. "Association of miR-125b, miR-17 and let-7c Dysregulations With Response to Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With Metastatic Colorectal Cancer." Cancer Genomics and Proteomics 17, no. 5 (2020): 605–13. https://doi.org/10.21873/cgp.20217.

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Background/Aim: MicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients. Patients and Methods: This retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR. Results: Down-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression-free and overall survival (p=0.055 and p=0.006). Conclusion: The results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 down-regulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.
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Palak, Ewelina, Weronika Lebiedzińska, Sławomir Anisimowicz, et al. "The Association between Bisphenol A, Steroid Hormones, and Selected MicroRNAs Levels in Seminal Plasma of Men with Infertility." Journal of Clinical Medicine 10, no. 24 (2021): 5945. http://dx.doi.org/10.3390/jcm10245945.

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Bisphenol A (BPA), the most common endocrine-disrupting chemical, has been associated with male reproductive dysfunctions. Recently, it has been shown that BPA may also affect miRNAs expression. Herein, we aimed to evaluate the association of BPA levels with steroid hormone concentration and circulating miRNAs levels to investigate the potential direct effect of BPA on homeostasis in the testis environment. The level of BPA in the seminal plasma of azoospermic men was significantly higher compared to the healthy control. The concentrations of estradiol (E2) and androstenedione (A) were significantly decreased in the seminal plasma of azoospermic men compared to the normospermic men. The levels of miR-let-7a, miR-let-7b, and miR-let-7c were significantly up-regulated, and the level of miR-518f was significantly down-regulated in the seminal plasma of the azoospermic men compared to the healthy control. The level of BPA correlated negatively with sperm concentration and normal semen morphology. A significant positive correlation was found between BPA levels and miR-let-7a and miR-let-7c levels, whereas BPA negatively correlated with miR-518f levels. Our results suggest that BPA may negatively affect sperm quality. Moreover, BPA correlated with the miR-let-7a, miR-let-7c, and miR-518f levels in seminal plasma, which suggests that BPA may act directly in seminal plasma, affecting the testicular environment.
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Perdas, Ewelina, Robert Stawski, Krzysztof Kaczka, and Maria Zubrzycka. "Analysis of Let-7 Family miRNA in Plasma as Potential Predictive Biomarkers of Diagnosis for Papillary Thyroid Cancer." Diagnostics 10, no. 3 (2020): 130. http://dx.doi.org/10.3390/diagnostics10030130.

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The most common histological type of thyroid cancer is papillary thyroid carcinoma (PTC). Radical resection of the thyroid gland is currently the recommended method of treatment. Almost 75% of thyroidectomies performed just for diagnostic purposes are benign. Thus, the confirmation of innovative and more precise noninvasive biomarkers holds promise for the detection of PTC, which may decrease the number of unnecessary thyroid lobectomies. In this work, using the droplet digital PCR (ddPCR) method, we have analyzed the level of five miRNAs (let-7a, let-7c, let-7d, let-7f, and let-7i) in the plasma of patients with PTC and compared them with those of a healthy control group to investigate whether miRNAs also have value in the management of PTC. Levels of four miRNAs, namely let-7a, let-7c, let-7d, and let-7f, were significantly higher in PTC patients than healthy controls. Thus, the analysis of circulating let-7 can be a useful tool and support the currently used methods for PTC diagnosis. However, our observation requires further research on a larger patient group.
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Habibi, Alireza, Nesa Bakhshi, Zeinab Moradi shoili, and Nour Amirmozafari. "Iron Oxide Nanoparticles Conjugated to Thiosemicarbazone Reduce the Survival of Cancer Cells by Increasing the Gene Expression of MicroRNA let-7c in Lung Cancer A549 Cells." Archives of Iranian Medicine 25, no. 12 (2022): 807–16. http://dx.doi.org/10.34172/aim.2022.126.

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Background: Cancer cells have a higher demand for iron to grow and proliferate. A new complex of iron nanoparticles and thiosemicarbazones was synthesized. Confirmation tests included UV-visible, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared (FTIR), X-ray diffraction (XRD) and zeta potential. Methods: MTT assay, flow cytometry and qRT-PCR were used to investigate anti-proliferative effect, amount of apoptosis and the effect of Fe3 O4 @Glu/BTSC on changes in gene expression of microRNA let-7c (let-7c), respectively. The specifications of Fe3 O4 @ Glu/BTSC were confirmed at 5 nm. Results: Fe3O4@Glu/BTSC was more effective than BTSC and Fe3 O4 on A549 cells (IC50=166.77 µg/mL) but its effect on healthy cells was smaller (CC50=189.15 µg/mL). The drug selectivity index (SI) was calculated to be 1.13. The initial apoptosis rate was 46.33% for Fe3 O4 @Glu/BTSC, 28.27% for BTSC and 26.02% for Fe3 O4 . BTSC and BTSC@Fe3 O4 inhibited the cell cycle progression in the Sub-G1 and S phases. let-7c expression was 6.9 times higher in treated cells compared to the control group. The expression rate was 2.2 with BTSC compared to the control group and 1.6 times for Fe3 O4. Conclusion: Fe3 O4 @Glu/BTSC has proper anti-proliferative effects against lung cancer cells by increasing the expression of let-7c and inhibiting the cell cycle with the apoptosis activation pathway.
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Küçüker, Kürşat, Hülya Aybek, Hakan Akça, et al. "The Role of microRNA in Overactive Bladder: Relationship and Clinical Correlation." Medicina 61, no. 3 (2025): 475. https://doi.org/10.3390/medicina61030475.

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Background and Objectives: This study aimed to determine the relationship between miRNAs and overactive bladder (OAB). We also aimed to reveal the diagnostic properties of miRNAs and their potential to predict responses to therapy. Materials and Methods: The study included 60 patients with OAB as the treatment group and 60 healthy individuals as the control group. The blood levels of 15 miRNAs in both groups were determined using PCR. Also, miRNAs with high diagnostic values were identified with receiver operating characteristic (ROC) curves. Finally, the Turkish-validated OAB questionnaire form was filled out before and after the treatment by the participants in the treatment group. In this way, the relationship between OAB score changes and miRNA levels was examined. Results: The let-7a, let-7c, let-7e, let-7f, and let-7g miRNA molecules in the treatment group were higher, with a high level of significance (p = 0.0001). Additionally, the miR-135b, miR-300, miR-372, miR-373, miR-381, miR-520a, miR-520d, and miR-520e miRNA molecules were found to be statistically higher in the control group (p = 0.0001). In addition, let-7c (area under curve [AUC] = 0.985) and the let-7c + miR-381 combination (area under curve [AUC] = 1) were the highest values in the ROC analysis. Finally, after treatment in the patient group, a significant difference was detected in both miRNAs (let-7f and miR-135b) in patients with clinical improvements of 50% and above in the OAB score. Conclusions: miRNAs may help elucidate the pathophysiology of OAB. They may shed light on diagnosis and evaluation of treatment effectiveness.
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Zhao, Shaoyun, Zhe Gong, Jing Zhang, et al. "Elevated Serum MicroRNA Let-7c in Moyamoya Disease." Journal of Stroke and Cerebrovascular Diseases 24, no. 8 (2015): 1709–14. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.01.041.

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Niculae, Andrei Marian, Maria Dobre, Vlad Herlea, et al. "Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis." Life 12, no. 10 (2022): 1638. http://dx.doi.org/10.3390/life12101638.

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Increased insulin-like growth factor (IGF) axis activity is associated with the development and progression of different types of malignancies, including colorectal cancer (CRC). MicroRNAs (miRNAs) belonging to the let-7 family have been reported to target genes involved in this axis and are known as tumor suppressors. In this study, in silico bioinformatic analysis was performed to assess miRNA–mRNA interactions between eight miRNAs belonging to the let-7 family and genes involved in the IGF signaling pathway, coding for receptors and substrates. miRNAs’ expression analysis revealed that hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, hsa-let- 97 7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, and hsa-let-7g-5p were significantly down-regulated in 25 CRC tumoral tissues (T) compared to the corresponding adjacent peritumoral tissues (PT). Moreover, our results showed an upregulation of miR-let-7e-5p in CRC tissues with mutations in KRAS codon 12 or 13, and, for the first time, found a specific dysregulation of let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, and let-7i-5p in CRC with perineural invasion. Our results sustain the relationship between the IGF axis, let-7 miRNAs, and CRC and suggest an association between the expression of these miRNAs and perineural invasion.
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Obaidi, Ismael, Alfonso Blanco Fernández, and Tara McMorrow. "Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism." International Journal of Molecular Sciences 23, no. 17 (2022): 9569. http://dx.doi.org/10.3390/ijms23179569.

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Targeted therapies are the most attractive options in the treatment of different tumours, including kidney cancers. Such therapies have entered a golden era due to advancements in research, breakthroughs in scientific knowledge, and a better understanding of cancer therapy mechanisms, which significantly improve the survival rates and life expectancy of patients. The use of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) as an anticancer therapy has attracted the attention of the scientific community and created great excitement due to its selectivity in targeting cancerous cells with no toxic impacts on normal tissues. However, clinical studies disappointingly showed the emergence of resistance against TRAIL. This study aimed to employ curcumin to sensitise TRAIL-resistant kidney cancerous ACHN cells, as well as to gain insight into the molecular mechanisms of TRAIL sensitization. Curcumin deregulated the expression of apoptosis-regulating micro Ribonucleic Acid (miRNAs), most notably, let-7C. Transfecting ACHN cells with a let-7C antagomir significantly increased the expression of several cell cycle protein, namely beta (β)-catenin, cyclin dependent kinase (CDK)1/2/4/6 and cyclin B/D. Further, it overexpressed the expression of the two key glycolysis regulating proteins including hypoxia-inducible factor 1-alpha (HIF-1α) and pyruvate dehydrogenase kinase 1 (PDK1). Curcumin also suppressed the expression of the overexpressed proteins when added to the antagomir transfected cells. Overall, curcumin targeted ACHN cell cycle and cellular metabolism by promoting the differential expression of let-7C. To the best of our knowledge, this is the first study to mechanistically report the cancer chemosensitisation potential of curcumin in kidney cancer cells via induction of let-7C.
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Tsai, Yi-Shan, Ming-Lun Yeh, Pei-Chien Tsai, et al. "Clusters of Circulating let-7 Family Tumor Suppressors Are Associated with Clinical Characteristics of Chronic Hepatitis C." International Journal of Molecular Sciences 21, no. 14 (2020): 4945. http://dx.doi.org/10.3390/ijms21144945.

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Hepatitis C virus (HCV) infections can cause permanent liver-related diseases, including hepatocellular carcinoma (HCC). Low mortality and incidence of HCC have been observed in patients with chronic hepatitis C undergoing direct-acting antiviral therapy. Tumor suppressive let-7 family members are down-regulated in HCC. The present study, therefore, aimed to investigate whether expression levels for the full spectrum of let-7 family members (let-7a, 7b, 7c, 7d, 7e, 7f, 7g, 7i, and miR-98) in the circulatory system are useful as surveillance biomarkers for liver-related diseases to monitor treatment efficacy during HCV infection. To this end, we measured the levels of mature circulating let-7 family members using quantitative reverse transcription-PCR in 236 patients with HCV infection, and 147 age- and sex-matched controls. Using hierarchical cluster analysis and principal component analysis, three clusters were obtained after measuring expression levels of let-7 family members in the patients and controls. Cluster 1 included let-7a/d/e/g, Cluster 2 comprised let-7b and let-7i, and Cluster 3 comprised let-7c/f/miR-98. Let-7b/c/g represented the three clusters and showed the best survival response to liver cancer when analyzed with respect to patient data. Therefore, considering the circulating levels of let7 b/c/g as representatives of the let-7 family may facilitate effective monitoring of liver-related disease.
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Zhan, Min, Qiang Qu, Guo Wang, et al. "Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1." Asian Pacific Journal of Cancer Prevention 14, no. 1 (2013): 387–92. http://dx.doi.org/10.7314/apjcp.2013.14.1.387.

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Шляхтунов, Е. А. "MicroRNA Expression in Circulating Cancer Cells During Treatment with Trastuzumab in Patients with Breast Cancer with Overexpression of the Epidermal Growth Factor Receptor HER2/neu." Евразийский онкологический журнал 11, no. 4 (2023): 322–36. http://dx.doi.org/10.34883/pi.2023.11.4.019.

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Цель. Изучить экспрессию микроРНК в циркулирующих опухолевых клетках как маркеров химиорезистентности у пациенток, страдающих раком молочной железы с гиперэкспрессией рецептора эпидермального фактора роста HER2-neu. Материалы. Объектом исследования является периферическая кровь 40 пациентов (а именно циркулирующие опухолевые клетки), страдающих раком молочной железы с гиперэкспрессией HER2-neu. После выделения и лизирования ЦОК определяли экспрессию генов множественной лекарственной устойчивости ABC-транспортеров и спектра микроРНК в течение 12 месяцев терапии трастузумабом. Результаты. Циркулирующие опухолевые клетки у пациентов, страдающих раком молочной железы, характеризуются генетической и фенотипической гетерогенностью, проявляющейся изменением уровня экспрессии микроРНК (miR-21, miR-155, miR-221, miR-210, miR-542-3p, miR-31, miR-17, let-7a, let-7c), онкогенов HER2-neu, BIRC5, а также генов химиорезистентности семейства ABC-транспортеров (ABCB1, ABCC1, ABCC5, ABCC10, ABCG2). Изменения экспрессии микроРНК в ЦОК выявлены в 94,0% случаев, при этом экспрессия онкосупрессорных микроРНК (miR-31, miR-17, let-7a, let-7c) характеризуется низким уровнем, онкогенных микроРНК (miR-21, miR-155, miR-221, miR-542-3p) – высоким (p<0,05). Высокий уровень экспрессии онкогенных микроРНК miR-21 (р=0,006), miR-155 (р=0,009) и miR-542-3p (р=0,005) в ЦОК коррелирует с HER2-neu-положительным РМЖ и худшим прогнозом. Сохранение в периферической крови ЦОК с высокой экспрессией онкогенных микроРНК статистически значимо увеличивает риск прогрессирования рака молочной железы на фоне терапии трастузумабом (ОР 18,33; 95% ДИ 2,672–125,810). Заключение. Отсутствие эффекта от терапии трастузумабом может быть обусловлено у части пациентов развитием резистентности ЦОК к моноклональному антителу трастузумабу, что подтверждается сохранением и наличием в периферической крови ЦОК (в 37,5% случаев), в которых определяются высокие уровни экспрессии онкогенных микроРНК, главным образом miR-21 (≥4,17), miR-221 (≥4,96), miR-542-3(p≥6,15), с отсутствием или низким уровнем экспрессии онкосупрессорных микроРНК (miR-31, miR-17, let-7a, let-7c). Purpose. To study the expression of microRNAs in circulating tumor cells as markers of chemoresistance in patients suffering from breast cancer with overexpression of the epidermal growth factor receptor HER2-neu. Materials. The peripheral blood of 40 patients (circulating tumor cells) suffering from breast cancer with overexpression of HER2-neu. After isolation and ligation of CCC, the expression of multidrug resistance genes of ABC transporters and the microRNA spectrum was determined during 12 months of trastuzumab therapy. Results. Circulating tumor cells in patients with breast cancer are characterized by genetic and phenotypic heterogeneity, manifested by changes in the level of microRNA expression (miR-21, miR-155, miR-221, miR-210, miR-542-3p, miR-31, miR-17, let-7a, let- 7c), oncogenes HER2-neu, BIRC5, as well as chemoresistance genes of the ABC transporter family (ABCB1, ABCC1, ABCC5, ABCC10, ABCG2). Changes in microRNA expression in the CCC were detected in 94.0% of cases, while the expression of oncosuppressive microRNAs (miR-31, miR-17, let-7a, let-7c) is characterized by a low level, oncogenic microRNAs (miR-21, miR-155, miR-221, miR-542-3p) is high (p<0.05). The high level of expression of oncogenic miR-21 microRNAs (p=0.006), miR-155 (p=0.009) and miR-542-3p (p=0.005) in the CCC correlates with HER2-neu-positive breast cancer and a worse prognosis. Preservation of CCC in peripheral blood with high expression of oncogenic microRNAs significantly increases the risk of breast cancer progression during trastuzumab therapy (HR 18.33; 95% CI 2.672–125.810). Conclusion. The lack of effect from trastuzumab therapy may be due to the development of CCC resistance to the monoclonal antibody trastuzumab in some patients, which is confirmed by the preservation and presence of CCC in peripheral blood (in 37.5% of cases), in which high levels of expression of oncogenic microRNAs are determined, mainly miR-21 (≥4.17), miR-221 (≥4.96), miR-542-3(p≥6.15), with no or low expression of oncosuppressive microRNAs (miR-31, miR-17, let-7a, let-7c).
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Li, Jieyan, Lei Hou, Rong Zhao, and Liying Zou. "Potential Use of Anti-Cancer Drugs for Treatment of Preeclampsia by Targeting the miRNA-IGF1R-PI3K-AKT Axis." Evidence-Based Complementary and Alternative Medicine 2022 (August 22, 2022): 1–8. http://dx.doi.org/10.1155/2022/3883082.

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Aim. Preeclampsia (PE) belongs to hypertensive disorders of pregnancy (HDP), which can cause maternal death worldwide. This study aimed to identify the miRNA-mRNA-associated ceRNA network and to find new treatment schedules for PE. Methods. 4 microarray datasets were downloaded from the Gene Expression Omnibus database. We obtained 1737 differentially expressed mRNAs (865 upregulated and 872 downregulated) and 148 differentially expressed miRNAs (76 upregulated and 72 downregulated) from the placenta tissues of PE, respectively. Functional enrichment analyses of DEmRNAs were performed. The regulatory relationship between DEmiRNAs and DEmRNA was predicted via related databases. An miRNA-mRNA regulatory network was constructed. Results. hsa-let-7c and IGF1R were identified as potential regulators for PE, and function enrichment analysis showed that the PI3K-Akt signaling pathway was closely related. Therefore, ceRNAs might regulate the PI3K-Akt signaling pathway via the upregulation of IGF1R by binding to hsa-let-7c, affecting invasion of trophoblast, angiogenesis, and proinflammation in PE. Further study demonstrated that anticancer drugs including the PI3K inhibitor, AKT inhibitor, and IGF-1 inhibitor might be a potential solution for PE treatment. Conclusions. The hsa-let-7c/IGF1R axis might affect the PI3K-Akt signaling pathway which is involved in the pathogenesis of PE, and inhibitors targeting this pathway might be used for PE treatment.
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Ribeiro dos Santos, Ândrea Kely Campos, Cristina Maria Duarte Valente, Milene Raiol de Moraes, Antonio André Conde Modesto, and Leandro Magalhães. "Biomarcadores preditivos em tecidos bucais e suas implicações na saúde em uma população miscigenada da Amazônia." Amazônica - Revista de Antropologia 13, no. 2 (2021): 731. http://dx.doi.org/10.18542/amazonica.v13i2.7759.

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Os casos de câncer aumentaram mundialmente. Estimam-se, para o Brasil, 14.700 novos casos de carcinoma de células escamosas oral (CCEO) para o biênio 2018-2019. O câncer pode ser prevenido com estilo de vida saudável e com análises de microRNAs, biomarcadores envolvidos na oncogênese. O objetivo deste estudo foi avaliar a associação do nível de expressão do microRNAs da família Let-7 (miR-let-7c) relacionando-o a fatores epigenéticos e socioeconômicos de indivíduos residentes no município de Belém (Pará). A amostra, apesar da heterogeneidade, não apresentou diferenças estatísticas na expressão do microRNA let-7c mostrando que, no processo da formação da população de Belém, este biomarcador não sofre influência da ancestralidade genômica, fazendo dele, um bom marcador de risco, podendo, ser utilizado como ferramenta em estudos comparativos relacionados ao câncer ou doenças infectocontagiosas. Um vasto campo e uma infinidade de biomarcadores podem ainda ser identificados e analisados, resultando em tratamentos menos invasivos, com melhores prognósticos.
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Brandão-Lima, Paula N., Gabrielli B. de de Carvalho, Tanyara B. Payolla, et al. "Circulating microRNAs Showed Specific Responses According to Metabolic Syndrome Components and Sex of Adults from a Population-Based Study." Metabolites 13, no. 1 (2022): 2. http://dx.doi.org/10.3390/metabo13010002.

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microRNAs (miRNAs) regulate several metabolic pathways and are potential biomarkers for early risk prediction of metabolic syndrome (MetS). Our aim was to evaluate the levels of 21 miRNAs in plasma according to MetS components and sex in adults. We employed a cross-sectional study of 192 adults aged 20 to 59 years old from the 2015 Health Survey of São Paulo with Focus in Nutrition. Data showed reduced levels of miR-16 and miR-363 in women with MetS; however, men with one or more risk factors showed higher levels of miR-let-7c and miR-30a. Individuals with raised waist circumference showed higher levels of miR-let-7c, miR-122, miR-30a, miR-146a, miR-15a, miR-30d and miR-222. Individuals with raised blood pressure had higher miR-30a, miR-122 and miR-30a levels. Plasma levels of four miRNAs (miR-16, miR-363, miR-375 and miR-486) were lower in individuals with low HDL-cholesterol concentrations. In addition, plasma levels of five miRNAs (miR-122, miR-139, miR-let-7c, miR-126 and miR-30a) were increased in individuals with high fasting plasma glucose and/or insulin resistance. Our results suggest that the pattern of miRNA levels in plasma may be a useful early biomarker of cardiometabolic components of MetS and highlight the sex differences in the plasma levels of miRNAs in individuals with MetS.
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Gururajan, A., M. E. Naughton, K. A. Scott, et al. "MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c." Translational Psychiatry 6, no. 8 (2016): e862-e862. http://dx.doi.org/10.1038/tp.2016.131.

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Emmrich, Stephan, Kerstin Henke, Zhe Li, et al. "Deciphering the Role of Mir-99∼125 clusters in the Hematopoietic System." Blood 118, no. 21 (2011): 213. http://dx.doi.org/10.1182/blood.v118.21.213.213.

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Abstract Abstract 213 Three human miR-99∼125 clusters, each containing one miR-99/100, let-7 and miR-125 family member in identical polycistronic configuration, are located within or next to long non-coding RNA (lncRNA) host genes on distinct chromosomal regions. The cluster miRNAs are highly expressed in hematopoietic stem and progenitor cells (HSPCs). The individual importance for stem cell homeostasis and differentiation of let-7 and miR-125 was extensively studied. However, genomic redundancy and high phylogenetic conservation of this ncRNA ensemble suggest a functionally linked role on gene regulatory networks, which remained elusive. Here we describe a synthetic phenotype pattern of the miR-99∼125 clusters on the hematopoietic system. Expression profiling in CD34+-HSPCs (n=2) and megakaryocytes (n=1) from healthy donors, in sorted leukemic blasts from patients with Down syndrome (DS) acute megakaryoblastic leukemia (AMKL; n=5), DS-transient leukemia (n=4), non-DS-AMKL (n=3), acute myeloid leukemia (AML FAB M5; n=2) and in various cell lines (CMK, CMY, Meg01, M07e [all megakaryoblastic leukemia], K562, KG1α, NB4, THP1 and Jurkat) indicated an enrichment of mature miR-99∼125 miRNAs and their lncRNA host genes in acute megakaryoblastic leukemia. Quantification of primary miRNA/mRNA transcripts indicated that intronic miR-99∼125 miRNAs are produced in one primary transcript with their lncRNA host genes C21ORF34 and MIR100HG. 5'RACE revealed the transcription start sites of those transcripts, which allowed mapping of phylogenetically conserved transcription factor binding sites in their promoter regions. Subsequent chromatin immunoprecipitation (ChIP) and luciferase reporter assays confirmed the binding and positive regulation by the leukemogenic transcription factor and stem cell regulator HOXA10. Retroviral overexpression of miR-99∼125 cluster miRNAs in cord blood (CB)-HSPCs showed a recurrent phenotype. The tricistron (miR-99a/let-7c/miR-125b-2) and miR-125b-2 alone accelerated proliferation during megakaryocytic, neutrophilic and monocytic in vitro differentiation, while let-7c and miR-99a/let-7c blocked proliferation. Likewise, common myeloid (CMP) and megakaryocytic/erythroid progenitors (MEP) were expanded upon tricistron (CMP: 1.5-fold; MEP: 2-fold increase relative to control) and miR-125b-2 (CMP: 1.6-fold; MEP: 2.4-fold increase relative to control) overexpression and reduced upon let-7c (CMP: 2.1-fold; MEP: 2.5-fold reduction relative to control) and miR-99a/let-7c (CMP: 2.2-fold; MEP: 3-fold reduction relative to control) overexpression. Inversely, during induced megakaryocytic differentiation stable inhibition of miR-125b using sponge-technology (SP-miR125) or shRNA-mediated downregulation of the C21ORF34 host gene conferred a selective growth disadvantage (SP-miR125: 1.6-fold; shC21ORF34: 1.7-fold reduction relative to control) and inhibited colony-formation of AMKL cell lines (SP-miR125: 1.4-fold; shC21ORF34: 2-fold reduction relative to control) and CB-HSCs (SP-miR125: 1.7-fold; shC21ORF34: 3.7-fold reduction relative to control). Ectopic expression or stable inhibition of miR-99a alone had no effect in any assay. Collectively we deciphered the functional linkage of miR-99/100, let-7 and miR-125, which are produced from one primary transcript with their lncRNA host genes. The stem cell regulator HOXA10 acts upstream of this ncRNA ensemble. Our study creates a microRNA interaction network, wherein miR-125b dominates let-7 to induce proliferation and expansion of CMPs and MEPs, favoring megakaryoblastic leukemia. This suggests an epistatic circuit regulating stemness and developmental fate. Disclosures: No relevant conflicts of interest to declare.
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Pelosi, A., S. Careccia, V. Lulli, et al. "miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia." Oncogene 32, no. 31 (2012): 3648–54. http://dx.doi.org/10.1038/onc.2012.398.

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Zhu, X.-M., L.-J. Wu, J. Xu, R. Yang, and F.-S. Wu. "Let-7c MicroRNA Expression and Clinical Significance in Hepatocellular Carcinoma." Journal of International Medical Research 39, no. 6 (2011): 2323–29. http://dx.doi.org/10.1177/147323001103900631.

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Fassan, Matteo, Deborah Saraggi, Laura Balsamo, et al. "Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis." Oncotarget 7, no. 4 (2015): 4915–24. http://dx.doi.org/10.18632/oncotarget.6642.

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Bozgeyik, Esra. "Bioinformatic Analysis and in Vitro Validation of Let-7b and Let-7c in Breast Cancer." Computational Biology and Chemistry 84 (February 2020): 107191. http://dx.doi.org/10.1016/j.compbiolchem.2019.107191.

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Brennan, Eoin P., Karen A. Nolan, Emma Börgeson та ін. "Lipoxins Attenuate Renal Fibrosis by Inducing let-7c and Suppressing TGFβR1". Journal of the American Society of Nephrology 24, № 4 (2013): 627–37. http://dx.doi.org/10.1681/asn.2012060550.

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LI, XIN-XIN, SHU-YAN GAO, PING-YU WANG, et al. "Reduced expression levels of let-7c in human breast cancer patients." Oncology Letters 9, no. 3 (2015): 1207–12. http://dx.doi.org/10.3892/ol.2015.2877.

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Wang, Ping-Yu, Yun-Xiao Sun, Shuai Zhang, et al. "Let-7c inhibits A549 cell proliferation through oncogenic TRIB2 related factors." FEBS Letters 587, no. 16 (2013): 2675–81. http://dx.doi.org/10.1016/j.febslet.2013.07.004.

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40

McWhorter, Erin S., Rachel C. West, Jennifer E. Russ, Asghar Ali, Quinton A. Winger, and Gerrit J. Bouma. "LIN28B regulates androgen receptor in human trophoblast cells through Let‐7c." Molecular Reproduction and Development 86, no. 9 (2019): 1086–93. http://dx.doi.org/10.1002/mrd.23226.

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Nguyen, Nga Thi, Luan Huu Huynh, Thuy Thi Chung Duong, Thanh Thi Ngoc Nguyen, and Hue Thi Nguyen. "Diagnostic and Prognostic Potential of Let-7 miRNAs in Breast Cancer: A Meta-Analysis." Trends in Sciences 22, no. 3 (2025): 9407. https://doi.org/10.48048/tis.2025.9407.

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MicroRNAs (miRNAs), particularly those in the let-7 family, show significant promise as diagnostic and prognostic biomarkers in breast cancer (BC). This meta-analysis systematically evaluates their diagnostic accuracy and prognostic value, addressing inconsistencies across previous studies. We searched PubMed, PMC, ScienceDirect and EMBASE databases for studies assessing let-7 miRNAs in BC. A total of 23 studies involving 8,249 participants were included. For diagnosis, the let-7 miRNA family demonstrated a pooled sensitivity of 0.87 (95 % CI: 0.80 - 0.92) and specificity of 0.76 (95 % CI: 0.62 - 0.86), with a diagnostic odds ratio (DOR) of 36.05 (95 % CI: 17.26 - 75.26) and an area under the curve (AUC) of 0.92 (95 % CI: 0.86 - 0.98). Subgroup analysis revealed that miR-202 in liquid biopsy samples from Asian populations showed the highest diagnostic accuracy (AUC: 0.98). For prognosis, low expression of let-7 miRNAs correlated with poorer survival outcomes, with a pooled hazard ratio (HR) for overall survival (OS) of 0.76 (95 % CI: 0.59 - 0.99). Notably, let-7a and let-7c were associated with aggressive BC subtypes. These findings underscore the let-7 family’s potential for BC diagnosis and prognosis, particularly miR-202 for non-invasive detection. However, high heterogeneity across studies was noted due to variations in methods and populations. Future research should validate these findings in diverse populations and standardize detection methods to explore their clinical utility. HIGHLIGHTS Let-7 miRNAs demonstrate high diagnostic accuracy for breast cancer, with a sensitivity (87 %), specificity (76 %), and an AUC of 0.92. miR-202 shows the highest diagnostic potential, particularly in liquid biopsy samples from Asian populations (AUC: 0.98). Let-7a and let-7c are associated with poorer survival outcomes, highlighting their prognostic value in aggressive breast cancer subtypes (HR: 0.76 for OS). Meta-regression identifies RT-PCR chemistries (TaqMan > SYBR Green) as a major source of heterogeneity in diagnostic performance. These findings support let-7 miRNAs as promising non-invasive biomarkers for early detection and the personalized management of breast cancer. GRAPHICAL ABSTRACT
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Nelson, Shannon R., Sandra Roche, Maura Cotter, et al. "Genomic Profiling and Functional Analysis of let-7c miRNA-mRNA Interactions Identify SOX13 to Be Involved in Invasion and Progression of Pancreatic Cancer." Journal of Oncology 2020 (December 24, 2020): 1–11. http://dx.doi.org/10.1155/2020/2951921.

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Background. Pancreatic cancer is a devastating disease; its lethality is related to rapid growth and tendency to invade adjacent organs and metastasize at an early stage. Objective. The aim of this study was to identify miRNAs and their gene targets involved in the invasive phenotype in pancreatic cancer to better understand the biological behaviour and the rapid progression of this disease. Methods. miRNA profiling was performed in isogenic matched high invasive and low-invasive subclones derived from the MiaPaCa-2 cell line and validated in a panel of pancreatic cancer cell lines, tumour, and normal pancreas. Online miRNA target prediction algorithms and gene expression arrays were used to predict the target genes of the differentially expressed miRNAs. miRNAs and potential target genes were subjected to overexpression and knockdown approaches and downstream functional assays to determine their pathological role in pancreatic cancer. Results. Differential expression analysis revealed 10 significantly dysregulated miRNAs associated with invasive capacity (Student’s t-tests; P value <0.05; fold change = ±2). The expression of top upregulated miR-135b and downregulated let-7c miRNAs correlated with the invasive abilities of eight pancreatic cancer cell lines and displayed differential expression in pancreatic cancer and adjacent normal tissue specimens. Ectopic overexpression of let-7c decreased proliferation, invasion, and colony formation. Integrated analysis of miRNA-mRNA using in silico algorithms and experimental validation databases identified four putative gene targets of let-7c. One of these targets, SOX13, was found to be upregulated in PDAC tumour compared with normal tissue in TCGA and an independent data set by qPCR and immunohistochemistry. RNAi knockdown of SOX13 reduced the invasion and colony formation ability of pancreatic cancer cells. Conclusion. The identification of key miRNA-mRNA gene interactions and networks provide potential diagnostic and therapeutic strategies for better treatment options for pancreatic cancer patients.
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Mishra, Manoj K., Emanuele Loro, Kasturi Sengupta, Steve D. Wilton, and Tejvir S. Khurana. "Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction." PLOS ONE 12, no. 10 (2017): e0182676. http://dx.doi.org/10.1371/journal.pone.0182676.

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Emmrich, Stephan, Sarva Keihani, Dirk Reinhardt, and Jan-Henning Klusmann. "Members of the Mir-99/100~125 Tricistrons Cooperatively Induce a Pre-Leukemic Myeloproliferative Disorder." Blood 126, no. 23 (2015): 3579. http://dx.doi.org/10.1182/blood.v126.23.3579.3579.

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Abstract MicroRNAs (miRNAs) reflect the best studied class of regulatory non-coding RNAs (ncRNAs), which control genetic networks with key cellular functions. In vertebrate genomes, a significant number of miRNA genes are located closely adjacent to each other in miRNA polycistrons. The mature miRNAs of the three human miR-99/100~125 clusters, each containing one miR-99/100, let-7 and miR-125 family member in identical polycistronic configuration, are processed from one single transcript and are highly expressed in acute promyelocytic leukemia (APL). Expression profiling by qPCR in sorted murine hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), megakaryocytic erythroid progenitors (MEPs) and granulocytic monocytic progenitors (GMPs) revealed high expression levels of miR-99/100 and miR-125 family members in HSCs and CMPs. However, the consequences of the coordinated expression of the miRNAs belonging to different seed families on self-renewal and proliferation of HSCs and myeloid progenitors and their contribution to the pathogenesis of APL are not well understood. To elucidate the genetic interactive network of miR-99/100~125 miRNAs and the role of each individual miRNA within this network, we generated a set of eight different constructs covering any permutation of miRNA family members from the two miR-99/100~125 clusters on hsa11 and hsa21 (miR-99a, miR-125b-2, let-7c, miR-99a/let-7c, miR-100/miR-125b-1, let-7a-2/miR-125b-1, miR-100/let-7a-2/miR-125b-1 and miR-99a/let-7c/miR-125b-2). Lentiviral overexpression of these constructs in human hematopoietic stem and progenitor cells (HSPCs) resulted in a significant reduction of monocytic/macrophage colony-forming units (CFU-M; 2.2-2.8-fold, p≤0.05) and granulocytic CFU-Gs (2-4.3-fold, p≤0.05) in methylcellulose-based CFU assays exclusively for miR-125-containing bi-/tricistronic constructs (miR-100/miR-125b-1, let-7a-2/miR-125b-1, miR-100/let-7a-2/miR-125b-1 and miR-99a/let-7c/miR-125b-2), but not for the single miRNA expression constructs. Accordingly, during myelomonocytic differentiation HSPCs transduced with those miR-125-containing bi-/tricistronic constructs gave rise to a major population of monomorphic, non-adherent cells devoid of granulocytic and monocytic markers, which was not present in single miRNA-transduced cells. In murine isogenic transplantation experiments (N=105), only the combined miRNA expression of miR-125b with let-7 and/or miR-99/100 led to the expansion and retention of immature Gr-1(low)/Mac-1(+)/B220(-) cells in the bone marrow (1.6-1.8fold; p≤0.01). Accordingly, either the CMP or GMP compartment of transplanted mice was expanded in miR-125-containing bi-/tricistronic constructs (CMPs 1.6-fold in let-7a-2/miR-125b-1, GMPs 1.8-1.9-fold in miR-100/miR-125b-1 and tricistrons; p≤0.01;), but not upon single miRNA overexpression (1.1-1.3-fold; p≥0.1). Global gene expression profiling of human HSPCs transduced with the eight miRNA constructs revealed a core expression signature commonly regulated by the four miR-125b-containing bi-/ tricistronic constructs (367 genes upregulated [>1.5-fold]; 417 genes downregulated). Strikingly, this core signature is enriched for genes with concordant expression in leukemic stem cells (LSCs) and HSCs (FDR q≤1.8x10-14). The genes of the core signature were not or only modestly affected in the context of the single miRNAs. Thus, the miR-99/100~125 tricistron miRNAs form an interaction network, wherein the combined activity of miR-125b with let-7 and/or miR-99/100 family members converged to induce a stem cell signature creating a synthetic phenotype. The synthetic phenotype can only be observed in the combination of two or all three miRNAs but not for each miRNA alone, and is generated by miR-99/100 and/or let-7 altering the hematologically dominant miR-125 phenotype. This interactive network might explain the genomic miR-99/100~125 clustering and reveals a novel cooperative mode to induce self-renewal and a differentiation block in myeloid progenitor cells, predisposing them to leukemic transformation in APL. Disclosures No relevant conflicts of interest to declare.
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Antón Aparicio, Luis M., Vanessa Medina, Manuel Valladares Ayerbes, et al. "Circulating microRNAs as potential biomarkers in patients with renal tumors." Journal of Clinical Oncology 30, no. 5_suppl (2012): 405. http://dx.doi.org/10.1200/jco.2012.30.5_suppl.405.

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405 Background: MicroRNAs (miRNAs), a class of small RNAs, have been intensely investigated recently because of their important regulatory role in gene expression. Circulating miARNs are potential biomarkers for cancer not only abundant in blood, but also very stable, which are important prerequisites as clinical biomarkers. Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in genitourinary renal tumors. The aim of this work is identify miRNAs potentially useful for CTC detection in blood samples from patients with renal tumors to assess their potential clinical significance. Methods: We examined blood levels of three miRNAs, let-7c, miR-200c and miR-31 in 48 patients with renal tumors with locally advanced or metastatic disease and 18 healthy persons using quantitative real-time PCR. The clinicopathologic characteristics of the population under consideration include among other: sex, age, tumor location, histological type, Fuhrman grade, tumor size, number of involved nodes, tumor stage, time to progression and overall survival. Results: We found that the median levels of miRNAs, let-7c, miR-200c and miR-31 were significantly higher in patients with renal tumors than those in healthy controls (p=.002, p=.000 and p=.004, respectively). Receiver-operator characteristic (ROC) curve analyses indicate that these blood miRNAs may be useful markers for discriminating patients with renal tumors from healthy controls (AUC=.750, AUC=.853 and AUC=.738, respectively). Conclusions: miRNAs in the circulation are relatively stable, very accessible, low invasive and easily testable biomarkers. Our results suggest let-7c, miR-200c and miR-31 as novel stable blood-based markers for renal cancer detection. This work was supported by Grants PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III.S. Díaz Prado is supported by an Isidro Parga Pondal research contract by Xunta de Galicia (A Coruña, Galicia, Spain). Cancer research in our laboratory is supported by the “Fundación do CHU A Coruña”.
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Emmrich, Stephan, Mareike Rasche, Jennifer Schöning та ін. "the miR-99∼125 Polycistrons Promote Leukemogenesis in a Cell-Context Dependent Manner by Shifting the Balance Between TGFβ- and Wnt-Signaling". Blood 120, № 21 (2012): 109. http://dx.doi.org/10.1182/blood.v120.21.109.109.

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Abstract Abstract 109 Three human miR-99∼125 clusters, each containing one miR-99/100, let-7 and miR-125 family member in identical polycistronic configuration, are located within or next to long non-coding RNA (lncRNA) host genes on distinct chromosomal regions. In this study, we investigated the integrative function of these three polycistron-miRNAs. Expression profiling in sorted leukemic blasts indicated an enrichment of mature miR-99∼125 miRNAs in acute megakaryoblastic leukemia (AMKL) and promyelocytic leukemia (APL). We demonstrated that intronic miR-99∼125 miRNAs are produced from one primary transcript with their lncRNA host genes and that the leukemogenic transcription factor and stem cell regulator HOXA10 acts as an upstream transcriptional activator. Therefore, we assessed the consequences of concerted activation of miR-125b, miR-99/100 and let-7 in the megakaryocytic and myelomonocytic system. During megakaryocytic in vitro differentiation of hematopoietic stem and progenitor cells (HSPCs), lentiviral overexpression of the tricistron (miR-99a/let-7c/miR-125b-2) or miR-125b-2 alone increased proliferation and survival of megakaryocytic cells. Megakaryocytic/erythroid progenitors (MEP) were expanded upon tricistron and miR-125b-2 overexpression, and not by miR-99a and/or let-7c overexpression. In an unbiased triple-transduction RGB-competition assay using distinct color-marked (red/green/blue) monocistronic miRNA constructs, miR-125b-2 alone or in combination with miR-99a or let-7 conferred a selective growth advantage to murine and human HSPCs. In murine transplantation experiments, only combined expression of all three cluster-miRNAs led to the expansion and retention of an immature Gr-1(low)/Mac-1(+)/B220(-) cell population in the bone marrow. Similarly when the miR-99a/let-7c/miR-125b-2 tricistron-transduced HSPCs differentiated along the myelomonocytic lineage (liquid culture and methylcellulose colony-forming assay), we observed a major cell population of monomorphic, non-adherent cells devoid of granulocytic and monocytic markers, which was not present in the miR-99a-, let-7c- or miR-125b-2 single transduced cells. Global gene expression profiling followed by qRT-PCR-validation of transduced HSPCs identified high confidence targets commonly or individually downregulated by the three miRNAs. Among these targets, we found TGFβ pathway agonists and Wnt antagonists to be enriched. miR-125b and -even stronger- the tricistron decreased the reporter activity of a SMAD response element in 293T cells treated with TGFβ and increased the activity of a TCF response element in synergy with a Wnt-activator (GSK3-inibitor). Western blotting and luciferase reporter assays demonstrated cooperative targeting of TGFBR1, ALK7, BMPR1a, BMPR2, SMAD2, SMAD4 and APC by the tricistron. Strikingly, inhibition of miR-125b by a lentiviral decoy sensitized TGFβ-resistant AMKL-cell lines (CMK and CMY) to TGFβ-mediated apoptosis and proliferation arrest. Conversely, overexpression of miR-125b or the tricistron rendered MV4:11 and NB4 cells resistance to TGFβ. miR-125b or the tricistron-transduced HSPCs displayed a marked increase in cell viability and cells in S-Phase upon TGFβ-treatment during megakaryocytic differentiation. The application of a TGFβ-inhibitor phenocopied the effects of miR-125b or the tricistron during megakaryocytic differentiation. These effects were not further enhanced by combined Wnt activation. In contrast, recapitulating the effects of the polycistron in the myelomonocytic lineage required Wnt-activation. Collectively we deciphered the functional linkage of miR-99/100, let-7 and miR-125, which are produced from one primary transcript with their lncRNA host genes and are regulated by the stem cell regulator HOXA10. Our study creates a microRNA interaction network, wherein the concerted action of the three miRNAs converges at the TGFβ pathway by a combinatorial block of this pathway. During myelomonocytic commitment only the combination of all polycistron-miRNAs enhanced Wnt signaling to inhibit differentiation. These synthetic phenotypes form an epistatic circuit regulating stemness and developmental fate. Disclosures: No relevant conflicts of interest to declare.
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Adoul, Z., S. Jafarinejed, A. Baumgartner, et al. "P064 Investigating the genotoxic effect of reduced glutathione, n-acetylcysteine, human umbilical cord-derived mesenchymal stem cell exosomes and let-7 miRNA mimics in human lymphocytes and EpiIntestinal cells." Journal of Crohn's and Colitis 18, Supplement_1 (2024): i334. http://dx.doi.org/10.1093/ecco-jcc/jjad212.0194.

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Abstract Background The current treatments for IBD frequently do not provide sufficient control over the disease, warranting the investigation of alternative therapeutic options with minimal risk of side effects. In IBD, the overgeneration and insufficient removal of reactive oxygen species (ROS) leads to oxidative stress. Reduced glutathione (GSH) and n-acetylcysteine (NAC) are antioxidants which may possess therapeutic potential in IBD, by modulating endogenous mechanisms that decrease ROS production or increase antioxidant enzymes. Additonally, exosomes from human umbilical cord blood derived mesenchymal stem cells (hucMSCs-exo) may be used to treat IBD. These are a subset of extracellular nanosized membrane vesicles which participate in intercellular communication by delivering their contents, such as functional miRNAs to recipient cells, thereby influencing the physiological and pathological processes in various diseases. The therapeutic potential of exosomes can be enhanced through the overexpression of the let-7 family of miRNAs. Methods The EpiIntestinal tissue model is a physiologically relevant predictor of drug-induced GI toxicity. EpiIntestinal cells and lymphocytes from 3 IBD patients were transfected with 50 μL miRNA mimics and inhibitors, and treated with 50μL hucMSC-exo, and 50 μL 1mM GSH and NAC. Next, in comparison to negative controls, single-stranded DNA damage was assessed in peripheral blood mononuclear cells (PBMCs) from IBD patients using the fast microplate DNA damage assay, and double-stranded DNA damage was assessed in EpiIntestinal cells using the alkaline Comet assay. In addition, the viability of healthy and IBD lymphocytes was assessed following treatment with selected concentrations of hucMSC-exo, GSH and NAC. Results Double-stranded DNA damage was significantly reduced in EpiIntestinal cells compared to the negative control following treatment with hucMSC-exo, GSH, NAC, and miRNA mimics for let-7a-5p, -7b-5p, -7c-3p, -7d-3p and -7d-5p. In addition, single-stranded DNA damage was reduced in IBD PBMCs compared to the negative control following treatment with hucMSC-exo, and let-7b-5p and -7c-3p mimics, but was increased following treatment with inhibitors for let-7b-5p, -7c-5p and two novel miRNAs. Additionally, GSH, NAC and hucMSC-exo increased cell viability in treated versus untreated lymphocytes from healthy individuals and IBD patients. Conclusion Selected concentrations of HucMSC-exo, GSH, NAC and/or let-7 miRNA mimics reduced DNA damage and increased cell viability in treated versus untreated cells which may reduce the risk of colorectal cancer in IBD patients. Acknowledgements Our gratitude goes to the MatTek Team for generously granting us a SMI-100-FT EpiIntestinal kit in support of this research.
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de Almeida, dos Anjos, Uno, et al. "Let-7 miRNA’s Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma." Cells 8, no. 11 (2019): 1452. http://dx.doi.org/10.3390/cells8111452.

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The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic markers in uterine leiomyosarcoma (LMS) patients. The miRNAs expression profile was assessed in 34 LMS and 13 normal myometrium (MM) paraffin-embedded samples. All let-7 family members showed downregulation in LMS. Our findings showed that patients with let-7e downregulation had worse overall survival (OS) and is an independent prognostic factor (hazard ratio [HR] = 2.24). In addition, almost half the patients had distant metastasis. LMS patients with downregulated let-7b and let-7d had worse disease-free survival (DFS); they are not independent prognostic factors (HR = 2.65). Patients’ ages were associated with let-7d, let-7e and let-7f (p = 0.0160) downregulation. In conclusion, all the let-7 family members were downregulated in LMS patients, and the greater the loss of expression of these molecules, the greater their relationship with worse prognosis of patients. Let-7e expression might influence the OS, while let-7b and le-7d might influence the DFS. The lowest expression levels of let-7d, let-7e, and let-7f were associated with the oldest patients. Our findings indicate strong evidence of let-7′s role as a potential prognostic biomarker in LMS.
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Keck, Bastian, Angelika Borkowetz, Julia Poellmann, et al. "Serum miRNAs Support the Indication for MRI-Ultrasound Fusion-Guided Biopsy of the Prostate in Patients with Low-PI-RADS Lesions." Cells 10, no. 6 (2021): 1315. http://dx.doi.org/10.3390/cells10061315.

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Multiparametric MRI (mpMRI) and targeted biopsy of the prostate enhance the tumor detection rate. However, the prediction of clinically significant prostate cancer (PCa) is still limited. Our study tested the additional value of serum levels of selected miRNAs in combination with clinical and mpMRI information for PCa prediction and classification. A total of 289 patients underwent targeted mpMRI-ultrasound fusion-guided prostate biopsy complemented by systematic biopsy. Serum miRNA levels of miRNAs (miR-141, miR-375, miR-21-5p, miR-320b, miR-210-3p, let-7c, and miR-486) were determined by quantitative PCR. Detection of any PCa and of significant PCa were the outcome variables. The patient age, pre-biopsy PSA level, previous biopsy procedure, PI-RADS score, and serum miRNA levels were covariates for regularized binary logistic regression models. The addition of miRNA expression of miR-486 and let-7c to the baseline model, containing only clinical parameters, increased the predictive accuracy. Particularly in patients with PI-RADS ≤3, we determined a sensitivity for detecting significant PCa (Gleason score≥7a corresponding to Grade group ≥2) of 95.2%, and an NPV for absence of significant PCa of 97.1%. This accuracy could be useful to support patient counseling in selected cases.
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Farhan, Mohd, Arshi Malik, Mohammad Ullah, et al. "Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs." International Journal of Molecular Sciences 20, no. 4 (2019): 800. http://dx.doi.org/10.3390/ijms20040800.

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Garcinol, a dietary factor obtained from Garcinia indica, modulates several key cellular signaling pathways as well as the expression of miRNAs. Acquired resistance to standard therapies, such as erlotinib and cisplatin, is a hallmark of non-small cell lung cancer (NSCLC) cells that often involves miRNA-regulated epithelial-to-mesenchymal transition (EMT). We used A549 cells that were exposed to transforming growth factor beta 1 (TGF-β1), resulting in A549M cells with mesenchymal and drug resistant phenotype, and report that garcinol sensitized resistant cells with mesenchymal phenotype to erlotinib as well as cisplatin with significant decrease in their IC50 values. It also potentiated the apoptosis-inducing activity of erlotinib in A549M and the endogenously mesenchymal H1299 NSCLC cells. Further, garcinol significantly upregulated several key EMT-regulating miRNAs, such as miR-200b, miR-205, miR-218, and let-7c. Antagonizing miRNAs, through anti-miRNA transfections, attenuated the EMT-modulating activity of garcinol, as determined by mRNA expression of EMT markers, E-cadherin, vimentin, and Zinc Finger E-Box Binding Homeobox 1 (ZEB1). This further led to repression of erlotinib as well as cisplatin sensitization, thus establishing the mechanistic role of miRNAs, particularly miR-200c and let-7c, in garcinol-mediated reversal of EMT and the resulting sensitization of NSCLC cells to standard therapies.
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