407032

MIR30C2

MicroRNAs (miRNAs), which negatively regulate protein expression by binding protein-coding mRNAs, have been integrated into cancer development and progression as either oncogenes or tumor suppressor genes. miR-30c was reported to be downregulated in several types of cancer. However, its role in human renal cell carcinoma (RCC) remains largely unknown. Here, we show that miR-30c is significantly downregulated in human RCC tissues and cell lines. We found that miR-30c downregulation could be induced by hypoxia in RCC cells in a hypoxia-inducible factors (HIFs) dependent manner. Repression of miR-30c through its inhibitor resulted in reduction of E-cadherin production and promotion of epithelial-mesenchymal transition (EMT), while overexpression of miR-30c inhibited EMT in RCC cells. We identified Slug as a direct target of miR-30c in RCC cells. Slug was upregulated in RCC tissues and its expression could be induced by hypoxia, which is consistent with downregulation of miR-30c by hypoxia. Forced overexpression of Slug in 786-O cells reduced E-cadherin production, and promoted EMT as well as cell migration. Moreover, Slug overexpression abrogated the inhibitory role of miR-30c in regulating EMT and cell migration, indicating miR-30c regulates EMT through Slug in RCC cells. Our findings propose a model that hypoxia induces EMT in RCC cells through downregulation of miR-30c, which leads to subsequent increase of Slug expression and repression of E-cadherin production, and suggest a potential application of miR-30c in RCC treatment.CI - (c) 2013 Japanese cancer Association.

MicroRNA (miR)30c has been identified as a tumor suppressor gene in numerous diseases. Aberrant miR30c expression has been associated with the invasion of different types of cancer. However, the potential mechanisms underlying the association between miR30c and invasion has been poorly elucidated in nonsmallcell lung cancer (NSCLC). In the present study, quantitative polymerase chain reaction demonstrated that the expression of miR30c was reduced in lung cancer specimens (n=85). Suppressing the expression of miR30c promoted the invasion of A549 cells, while overexpressed miR30c inhibited the invasion of A549 cells. Furthermore, aberrant miR30c expression was able to control the expression levels of markers (Ecadherin, snail and vimentin) of epithelial mesenchymal transition (EMT). In conclusion, miR30c regulated the invasion of NSCLC cells and low miR-30 levels induced EMT.

BACKGROUND: Aberrant expression of miRNAs was involved in tumor initiation, progression and metastasis in multiple cancers. Many kinds of microRNAs in esophageal squamous cell carcinoma (ESCC) have been researched, whereas miR-30c has not been included. METHODS: Firstly, we explored the expression of miR-30c in ESCC tissue and serum samples and its relations to the survival. To further investigate its effects on ESCC cells, we completed a series of experiments. We detected the effects of ectopic miR-30c expression on the proliferation, migration and invasion of ESCC cells in vitro. We identified the target role of SNAI1 in ESCC using Dual-luciferase reporter assay and western blot assay. RESULTS: The results showed miR-30c was significant down-regulated in ESCC tissues and cell lines. Clinically, we found lower miR-30c expression was significantly correlated with worse ESCC progression and survival. Also we clarified that miR-30c suppressed cell proliferation, invasion and epithelial to mesenchymal transition (EMT) of ESCC cell lines. What's more, we figured out that miR-30c inhibits ESCC biological behaviors and EMT progress by directly binding to the 3'-UTR of SNAI1. CONCLUSION: This study provides new insight into the mechanism responsible for the development of human ESCC. Therefore, miR-30c could be a promising biomarker and a therapeutic target for ESCC in the future.CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved.

epithelial-to-mesenchymal transition (EMT) plays a significant role in tubulointerstitial fibrosis, which is a hallmark of diabetic nephropathy. Thus, identifying the mechanisms of EMT activation could be meaningful. In this study, loss of miR-30c accompanied with increased EMT was observed in renal tubules of db/db mice and cultured HK2 cells exposed to high glucose. To further explore the roles of miR-30c in EMT and tubulointerstitial fibrosis, recombinant adeno-associated viral vector was applied to manipulate the expression of miR-30c. In vivo study showed that overexpression of miR-30c suppressed EMT, attenuated renal tubulointerstitial fibrosis and reduced proteinuria, serum creatinine, and BUN levels. In addition, Snail1 was identified as a direct target of miR-30c by Ago2 co-immunoprecipitation, luciferase reporter, and Western blot assays. Downregulating Snail1 by siRNA reduced high glucose-induced EMT in HK2 cells, and miR-30c mimicked the effects. Moreover, miR-30c inhibited Snail1-TGF-beta1 axis in tubular epithelial cells undergoing EMT and thereby impeded the release of TGF-beta1; oppositely, knockdown of miR-30c enhanced the secretion of TGF-beta1 from epitheliums and significantly promoted proliferation of fibroblasts and fibrogenesis of myofibroblasts, aggravated tubulointerstitial fibrosis, and dysfunction of diabetic nephropathy. These results suggest a protective role of miR-30c against diabetic nephropathy by suppressing EMT via inhibiting Snail1-TGF-beta1 pathway.CI - (c) 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.