Involvement of hepatitis B virus X gene (HBx) integration in hepatocarcinogenesis via a recombination of HBx/Alu core sequence/subtelomeric DNA

FEBS Lett. 2012 Sep 21;586(19):3215-21. doi: 10.1016/j.febslet.2012.06.039. Epub 2012 Jul 3.


The significance of hepatitis B virus (HBV) DNA-based integration in hepatocarcinogenesis is poorly understood. In the present study, we investigated whether the integration of HBV X gene (HBx) is involved in the event. Our finding showed that the integration of HBx fragment (316-462 bp/262-462 bp) was able to transform human immortalized normal liver LO2 cells using a cell model of HBx-integration. We identified that the recombination, HBx/Alu core sequence/subtelomeric DNA, was required for the transformation, which could be detected in 5 out of 44 clinical HBx-positive hepatocellular carcinoma tissues. Thus, we conclude that HBx integration is involved in the hepatocarcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements
  • Base Sequence
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Transformed
  • DNA, Neoplasm / genetics
  • DNA, Viral / genetics
  • Genes, Viral
  • Hep G2 Cells
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / pathogenicity*
  • Hepatitis B virus / physiology
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / virology
  • Models, Biological
  • Molecular Sequence Data
  • Recombination, Genetic
  • Telomere / genetics
  • Trans-Activators / genetics*
  • Viral Regulatory and Accessory Proteins
  • Virus Integration / genetics*


  • DNA, Neoplasm
  • DNA, Viral
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein