Hepatitis B virus X protein protects hepatoma and hepatic cells from complement-dependent cytotoxicity by up-regulation of CD46

Shuai Zhang; Changliang Shan; Wenjing Cui; Xiaona You; Yumei Du; Guangyao Kong; Fabao Gao; Lihong Ye; Xiaodong Zhang

doi:10.1016/j.febslet.2013.01.019

Hepatitis B virus X protein protects hepatoma and hepatic cells from complement-dependent cytotoxicity by up-regulation of CD46

FEBS Lett. 2013 Mar 18;587(6):645-51. doi: 10.1016/j.febslet.2013.01.019. Epub 2013 Feb 4.

Authors

Shuai Zhang¹, Changliang Shan, Wenjing Cui, Xiaona You, Yumei Du, Guangyao Kong, Fabao Gao, Lihong Ye, Xiaodong Zhang

Affiliation

¹ Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology and Biochemistry, College of Life Sciences, Nankai University, PR China.

PMID: 23391762
DOI: 10.1016/j.febslet.2013.01.019

Abstract

The involvement of hepatitis B virus X protein (HBx) in anti-complement-dependent cytotoxicity (CDC) activity during hepatocarcinogenesis is poorly understood. Here, we report that HBx is able to up-regulate membrane-bound complement regulatory protein CD46 in hepatoma cells and human immortalized liver cells through activating the promoter activity involving cAMP response element-binding protein (CREB)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. In contrast, the down-regulation of CD46 abolishes the resistance capability of hepatoma cells to CDC. Thus, we conclude that HBx contributes to the protection of hepatoma and hepatic cells from CDC by up-regulation of CD46.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / immunology
Carcinoma, Hepatocellular / virology*
Cell Line, Transformed
Complement Activation
Cyclic AMP / metabolism
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / metabolism
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism
Cytotoxicity, Immunologic
Dinoprostone / metabolism
Gene Expression Regulation, Neoplastic* / drug effects
Hepatitis B virus / genetics*
Hepatitis B, Chronic / genetics
Hepatitis B, Chronic / immunology
Hepatitis B, Chronic / virology
Host-Pathogen Interactions
Humans
Liver Neoplasms / genetics
Liver Neoplasms / immunology
Liver Neoplasms / virology*
Membrane Cofactor Protein / genetics*
Membrane Cofactor Protein / metabolism
Promoter Regions, Genetic
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects
Trans-Activators / genetics*
Trans-Activators / metabolism
Transcription, Genetic / drug effects
Viral Regulatory and Accessory Proteins

Substances

CD46 protein, human
CREB1 protein, human
Cyclic AMP Response Element-Binding Protein
Membrane Cofactor Protein
STAT3 Transcription Factor
STAT3 protein, human
Trans-Activators
Viral Regulatory and Accessory Proteins
hepatitis B virus X protein
Cyclic AMP
Cyclooxygenase 2
PTGS2 protein, human
Dinoprostone