miR-490-5p suppresses tumour growth in renal cell carcinoma through targeting PIK3CA

Biol Cell. 2016 Feb;108(2):41-50. doi: 10.1111/boc.201500033. Epub 2015 Dec 22.

Abstract

Background information: Dysregulated micro-RNAs have been reported in many human cancers, including renal cell carcinoma. Recent studies indicated that miR-490 is involved in tumour development and progression. However, the expression profile and function in renal cell carcinoma remains unknown.

Results: Herein, we showed that miR-490-5p was down-regulated in renal cell carcinoma tissues and cells compared with the adjacent normal tissues and normal cells. We also provided evidence that miR-490-5p acts as a tumour suppressor in renal carcinoma in a variety of in vitro and in vivo assays. Mechanistically, miR-490-5p was verified to directly bind to 3' UTR of the PIK3CA mRNA and reduce the expression of PIK3CA at both mRNA and protein levels, which further inhibits phosphatidylinositol 3-kinase/Akt signalling pathway. We further showed that knockdown of PIK3CA can block the growth inhibitory effect of miR-490-5p, and over-expression of PIK3CA can reverse the inhibitory effect of miR-490-5p on renal cancer cell tumourigenicity.

Conclusions: Taken together, our results indicated for the first time that miR-490-5p functions as a tumour suppressor in renal carcinoma by targeting PIK3CA.

Significance: Our findings suggest that miR-490-5p may be a potential gene therapy target for the treatment of renal cell carcinoma.

Keywords: PIK3CA; Renal cell carcinoma; Tumour suppressor; miR-490-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Class I Phosphatidylinositol 3-Kinases
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Mice, Nude
  • MicroRNAs / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism*

Substances

  • MIRN490 microRNA, human
  • MIRN490 microRNA, mouse
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Pik3ca protein, mouse