HBx-elevated SIRT2 promotes HBV replication and hepatocarcinogenesis

Biochem Biophys Res Commun. 2018 Feb 12;496(3):904-910. doi: 10.1016/j.bbrc.2018.01.127. Epub 2018 Jan 31.

Abstract

Sirtuin 2 (SIRT2) is a class III histone deacetylase that has been implicated to promote HCC development. However, the functional role of SIRT2 in HBV is still unclear. In this study, we found that HBV could upregulate SIRT2 expression. Additionally, HBx could activate SIRT2 promoter to upregulate the mRNA and protein level of SIRT2. Furthermore, we found that SIRT2 could facilitate HBV transcription and replication. Finally, we demonstrated that upregulation of SIRT2 by HBx promoted hepatocarcinogenesis. In summary, our findings revealed a novel function of SIRT2 in HBV and HBV-mediated HCC. First, SIRT2 could promote HBV replication. And then HBx-elevated SIRT2 could enhance the transformation of HBV-mediated HCC. Those findings highlight the potential role of SIRT2 in HBV and HBV-mediated HCC by interaction with HBx.

Keywords: HBx; HCC; SIRT2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Hepatitis B / metabolism
  • Hepatitis B / virology
  • Hepatitis B virus / physiology*
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology*
  • Sirtuin 2 / metabolism*
  • Virus Replication / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • LAMTOR5 protein, human
  • SIRT2 protein, human
  • Sirtuin 2