miR-26a promoted by interferon-alpha inhibits hepatocellular carcinoma proliferation and migration by blocking EZH2

Genet Test Mol Biomarkers. 2015 Jan;19(1):30-6. doi: 10.1089/gtmb.2014.0245.

Abstract

Backgrounds: Interferon (IFN)-α has been used to treat hepatocellular carcinoma (HCC). Here, we report that the IFN-α-induced microRNA-26a (miR-26a) can inhibit HCC proliferation and invasion by suppressing enhancer of zeste homologue 2 (EZH2) expression in tumor cells.

Materials and methods: First, the miR-26a transcription level was quantified by real-time quantitative PCR in the HCC specimens from IFN-α-treated HCC patients. Next, we transfected HepG2 cells with miR-26a mimics and miR control, and then we investigated the influence of miR-26a mimic transfection on HepG2 cell proliferation and invasion.

Results: It was shown that there was increased miR-26a accompanied with downregulated EZH2 expression in the HCC specimens, and EZH2 mRNA levels were inversely correlated with miR-26a expression. There was a dose-response correlation between the IFN-α dosage and EZH2 expression. In addition, the miR-26a mimic transfection decreased the EZH2 expression level significantly in the transfected HepG2 cells and inhibited HepG2 cell proliferation and invasion effectively.

Conclusion: Our results indicate that miR-26a exerts growth inhibition in HCC and that its inhibitory effect is mediated briefly by blocking EZH2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement*
  • Cell Proliferation*
  • Down-Regulation*
  • Enhancer of Zeste Homolog 2 Protein
  • Female
  • Hep G2 Cells
  • Humans
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Polycomb Repressive Complex 2 / biosynthesis*
  • Polycomb Repressive Complex 2 / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics

Substances

  • Interferon-alpha
  • MIRN26A microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2