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

Cell Death Dis. 2017 Jun 1;8(6):e2859. 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.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Binding Sites
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Survival Analysis
  • Transferases
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Zinc Finger E-box Binding Homeobox 2 / genetics*
  • Zinc Finger E-box Binding Homeobox 2 / metabolism

Substances

  • 3' Untranslated Regions
  • DLEU2 lncRNA, human
  • MIRN30b microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Transferases