MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence

Oncotarget. 2015 Oct 27;6(33):34446-57. doi: 10.18632/oncotarget.5920.

Abstract

Among a number of non-coding RNAs, role of microRNAs (miRNAs) in cancer cell proliferation, cancer initiation, development and metastasis have been extensively studied and miRNA based therapeutic approaches are being pursued. Prostate cancer (PCa) is a major health concern and several deregulated miRNAs have been described in PCa. miR-212 is differentially modulated in multiple cancers however its function remains elusive. In this study, we found that miR-212 is downregulated in PCa tissues when compared with benign adjacent regions (n = 40). Also, we observed reduced levels of circulatory miR-212 in serum from PCa patients (n = 40) when compared with healthy controls (n = 32). Elucidating the functional role of miR-212, we demonstrate that miR-212 negatively modulates starvation induced autophagy in PCa cells by targeting sirtuin 1 (SIRT1). Overexpression of miR-212 also leads to inhibition of angiogenesis and cellular senescence. In conclusion, our study indicates a functional role of miR-212 in PCa and suggests the development of miR-212 based therapies.

Keywords: SIRT1; autophagy; miR-212; microRNA; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Area Under Curve
  • Autophagy / physiology*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Cellular Senescence / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Laser Capture Microdissection
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / genetics*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • RNA, Small Interfering
  • ROC Curve
  • Sirtuin 1 / metabolism*
  • Transfection

Substances

  • Biomarkers, Tumor
  • MIRN212 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • SIRT1 protein, human
  • Sirtuin 1