C-terminal region of HBx is crucial for mitochondrial DNA damage

Cancer Lett. 2013 Apr 30;331(1):76-83. doi: 10.1016/j.canlet.2012.12.004. Epub 2012 Dec 12.

Abstract

HBx is strongly associated with hepatocellular carcinoma development through transcription factor activation and reactive oxygen species (ROSs) production. However, the exact role of HBx during hepatocellular carcinogenesis is not fully understood. Recently, it was reported that C-terminal truncated HBx is associated with tumor metastasis. In the present study, we confirmed that the C-terminal region of HBx is required for ROS production and 8-oxoguanine (8-oxoG) formation, which is considered as a reliable biomarker of oxidative stress. These results suggest ROS production induced by the C-terminal region of HBx leads to mitochondrial DNA damage, which may play a role in HCC development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Transformation, Neoplastic*
  • DNA Damage*
  • DNA, Mitochondrial / genetics*
  • Gene Expression Regulation
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Oxidative Stress
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured
  • Viral Regulatory and Accessory Proteins

Substances

  • DNA, Mitochondrial
  • RNA, Messenger
  • Reactive Oxygen Species
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • 8-hydroxyguanine
  • Guanine