MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma

FEBS J. 2011 Jun;278(12):2044-54. doi: 10.1111/j.1742-4658.2011.08120.x. Epub 2011 May 17.

Abstract

MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. Recently, microRNA-373 (miR-373) has been found to function as an oncogene in testicular germ cell tumors. In our study, we found that miR-373 is upregulated in human hepatocellular carcinoma (HCC) tissues as compared with adjacent normal tissues, and promotes the proliferation of the HCC cell lines HepG2 and QGY-7703 by regulating the transition between G(1)-phase and S-phase. The gene encoding the protein phosphatase 6 catalytic subunit (PPP6C ), a negative cell cycle regulator, was identified as a direct target gene of miR-373 by use of a fluorescent reporter assay. The mRNA and protein levels of PPP6C were both inversely correlated with the miR-373 expression level. Overexpression of PPP6C abolished the regulation of cell cycle and cell growth exercised by miR-373 in HepG2 cells. These results indicate that miR-373 plays an important role in the pathogenesis of HCC, and may be a new biomarker in HCC. Our results demonstrate that miR-373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR-373 may explain why the expression of miR-373 can promote HCC cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Oncogenes
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / genetics*
  • Up-Regulation

Substances

  • MIRN373 microRNA, human
  • MicroRNAs
  • Oligodeoxyribonucleotides, Antisense
  • Phosphoprotein Phosphatases
  • protein phosphatase 6