Regulation of HepG2 cell apoptosis by hepatitis C virus (HCV) core protein via the sirt1-p53-bax pathway

Virus Genes. 2015 Dec;51(3):338-46. doi: 10.1007/s11262-015-1253-2. Epub 2015 Oct 12.

Abstract

Hepatitis C virus (HCV) core protein stimulates many signaling pathways related to apoptosis inhibition resulting in hepatocellular carcinoma (HCC). It has been reported that sirt1 is involved in regulating apoptosis; therefore, we investigated the influence of HCV core protein on sirt1 expression and apoptosis in human HepG2 cells. Our study showed that HCV core protein inhibited apoptosis of HepG2 cells as well as caspase-3 expression and activity (P < 0.05). At the same time, sirt1 expression was increased at both the mRNA (P < 0.05) and protein (P < 0.05) levels. Furthermore, apoptosis inhibition was reversed when sirt1 was knocked down (P < 0.05). Our study provides further evidence that the sirt1-p53-Bax signaling pathway plays an important role in regulating the suppression of cell apoptosis induced by HCV core protein.

Keywords: Apoptosis; Bax; HCV core; p53; sirt1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Base Sequence
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / virology
  • Gene Knockdown Techniques
  • Hep G2 Cells / cytology
  • Hep G2 Cells / virology*
  • Hepacivirus / metabolism
  • Hepacivirus / physiology*
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / virology
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Sirtuin 1 / metabolism*
  • Sirtuin 1 / pharmacokinetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Viral Core Proteins / biosynthesis*
  • Viral Core Proteins / genetics
  • Viral Core Proteins / metabolism*
  • bcl-2-Associated X Protein / metabolism*

Substances

  • BAX protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Viral Core Proteins
  • bcl-2-Associated X Protein
  • nucleocapsid protein, Hepatitis C virus
  • SIRT1 protein, human
  • Sirtuin 1