miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma

FEBS Lett. 2012 Jul 30;586(16):2396-403. doi: 10.1016/j.febslet.2012.05.054. Epub 2012 Jun 7.

Abstract

MicroRNAs are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC). This study aims to explore the potential biological function of miR-376a, which was found to be inhibited after partial hepatectomy, in HCC. We discovered that miR-376a was frequently down-regulated in HCC cell lines and HCC tissues, while higher relative level of miR-376a was significantly associated with high serum AFP level. Over-expression of miR-376a not only inhibited proliferation but induced apoptosis in Huh7 cells. Additionally, p85α (PIK3R1) was identified as a direct and functional target of miR-376a in Huh7 cells. Moreover, we confirmed that p85α and miR-376a were inversely correlated in HCC. These findings suggest that down-regulation of miR-376a may contribute to the development of HCC by targeting p85α.

MeSH terms

  • Animals
  • Apoptosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Liver / pathology
  • Liver Neoplasms / metabolism*
  • Liver Regeneration
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Transfection
  • alpha-Fetoproteins / biosynthesis

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN376C microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • PIK3IP1 protein, human
  • alpha-Fetoproteins