The putative tumor suppressor microRNA-30a-5p modulates clear cell renal cell carcinoma aggressiveness through repression of ZEB2

Zhenhua Chen,Fangjian Zhou,Wei Chen,Zhiling Zhang,Jinhuan Wei,Junhang Luo,Yihui Pan,Yanping Liang,Zihao Feng,Yong Fang,Yong Huang,Junjie Cen,Jun Lu,Jiaxing Zhang

doi:10.1038/cddis.2017.252

Abstract

Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, can easily invade local tissues and metastasize, and is resistant to currently available treatments. Recent studies profiling microRNA expression in ccRCC have suggested miR-30a-5p may be deregulated in these cancer cells. To determine its role and mechanism of action in ccRCC, miR-30-5p expression levels were quantified and functions were analyzed using in vitro and in vivo experiments and bioinformatics. A decrease in miR-30a-5p expression was frequently noted in ccRCC cells and tissues. Importantly, low miR-30a-5p levels were significantly associated with a poor ccRCC patient prognosis. Stable overexpression of miR-30a-5p in 769-P cells was sufficient to prevent cellular proliferation and invasion in vitro and in vivo. Upon further examination, it was found that miR-30a-5p directly targeted the 3′-UTR of ZEB2 and suppressed ccRCC cell epithelial–mesenchymal transition. In addition, miR-30a-5p may be downregulated by the long non-coding RNA DLEU2. Taken together, these data reveal an important role for miR-30a-5p in the regulation of ccRCC proliferation and invasion, and indicate the potential for miR-30a-5p in applications furthering ccRCC prognostics and therapeutics.

Highlights

An increasing number of miRNAs have been reported to have functions in a diverse array of biological processes,[2,3,4] including human cancer development and progression.[5,6]
Downregulation of miR-30a-5p was a frequent occurrence in clear cell renal cell carcinoma (ccRCC) tissues, and low miR-30a-5p expression had a significant association with poor ccRCC patient survival
These results suggest that miR-30a-5p plays a crucial role in the growth, invasiveness and metastatic potential of ccRCC

Summary

Introduction

An increasing number of miRNAs have been reported to have functions in a diverse array of biological processes,[2,3,4] including human cancer development and progression.[5,6]. NAs, for example, miR-215, miR-200 s, miR-708, miR-205, miR-204, miR-199a and miR-141, have been reported to regulate ccRCC cell growth, apoptosis, migration and/or invasion,[13,14,15,16,17,18,19] suggesting miRNA dysfunction may be associated with renal carcinogenesis. Previous studies profiling miRNAs have noted the downregulation of a number of miRNAs in ccRCC One such downregulated miRNA identified was miR-30a-5p, which was one of the most influential in ccRCC pathogenesis.[20] It has been reported that ectopic expression of miR-30a-5p in ccRCC cells inhibits cellular migration and invasion. MiR-30a-5p has been demonstrated to suppress tumor growth in colon carcinomas,[21] decrease cellular proliferation and invasion of Ewing tumors,[22] inhibit cancer cell proliferation and induce apoptosis in liver cancers.[23] Altogether, these data indicate a potential tumor suppressive function for miR-30a-5p. The role of miR-30a-5p in ccRCC and the molecular mechanisms by which it functions remain to be delineated

Methods

Results

Conclusion