miR-372 regulates glioma cell proliferation and invasion by directly targeting PHLPP2

J Cell Biochem. 2015 Feb;116(2):225-32. doi: 10.1002/jcb.24949.

Abstract

MicroRNAs are known to be involved in carcinogenesis and tumor progression in glioma. Recently, microRNA-372 (miR-372) has been proved to play a substantial role in several human cancers, but its functions in glioma remain unclear. In this study, we confirmed that miR-372 was commonly upregulated in glioma cell lines and tissues. Downregulation of miR-372 markedly inhibited cell proliferation and invasion and induced G1/S arrest and apoptosis. Consistently, the xenograft mouse model also unveiled the suppressive effects of miR-372 knockdown on tumor growth. Further studies revealed that miR-372 modulated the expression of PHLPP2 by directly targeting its 3'-untranslated region (3'-UTR) and that miR-372 expression was inversely correlated with PHLPP2 expression in glioma samples. Silencing of PHLPP2 could rescue the inhibitory effect of miR-372 inhibitor. Moreover, miR-372 knockdown suppressed the phosphorylation levels of the major components of PI3K/Akt pathway including Akt, mTOR, and P70S6K. Taken together, our results suggest that miR-372 functions as an oncogenic miRNA through targeting PHLPP2 in glioma.

Keywords: GLIOMA; INVASION; PHLPP2; PROLIFERATION; miR-372.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Transplantation, Heterologous
  • Tumor Burden / genetics

Substances

  • 3' Untranslated Regions
  • MIRN372 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PHLPP2 protein, human
  • Phosphoprotein Phosphatases