The X protein of hepatitis B virus activates hepatoma cell proliferation through repressing melanoma inhibitory activity 2 gene.

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths globally. Chronic hepatitis B virus (HBV) infection accounts for over 75% of all HCC cases; however, the molecular pathogenesis of HCC is not well understood. In this study, we found that the expression of the newly identified gene melanoma inhibitory activity 2 (MIA2) was reduced by HBV infection in vitro and in vivo, and that HBV X protein (HBx) plays a major role in this regulation. Recent studies have revealed that MIA2 is a potential tumor suppressor, and that, in most HCCs, MIA2 expression is down-regulated or lost. We found that the knock-down of MIA2 in HepG2 cells activated cell growth and proliferation, suggesting that MIA2 inhibits HCC cell growth and proliferation. In addition, the over-expression of HBx alone induced cell proliferation, whereas MIA2 over-expression impaired the HBx-mediated induction of proliferation. Taken together, our results suggest that HBx activates hepatoma cell growth and proliferation through repression of the potential tumor suppressor MIA2.

• Authors: Yilin Xu, Yang Yang, Yanyan Cai, Fang Liu, Yingle Liu, Ying Zhu, Jianguo Wu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 416 Issue 3-4 Pg. 379-84 (Dec 16 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 22120627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier Inc.

Chemical References

• Antigens, Neoplasm
• MIA2 protein, human
• Neoplasm Proteins
• Trans-Activators
• Tumor Suppressor Proteins
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein

Topics

• Antigens, Neoplasm
• Carcinoma, Hepatocellular (pathology, virology)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Hepatitis B virus (metabolism)
• Humans
• Liver Neoplasms (pathology, virology)
• Neoplasm Proteins
• Trans-Activators (metabolism)
• Tumor Suppressor Proteins (antagonists & inhibitors, genetics)
• Viral Regulatory and Accessory Proteins