Oncotarget

Research Papers:

Hepatitis B virus X protein up-regulates C4b-binding protein α through activating transcription factor Sp1 in protection of hepatoma cells from complement attack

Guoxing Feng, Jiong Li, Minying Zheng, Zhe Yang, Yunxia Liu, Shuqin Zhang, Lihong Ye, Weiying Zhang and Xiaodong Zhang _

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Oncotarget. 2016; 7:28013-28026. https://doi.org/10.18632/oncotarget.8472

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Abstract

Guoxing Feng1, Jiong Li1, Minying Zheng1, Zhe Yang1, Yunxia Liu1, Shuqin Zhang1, Lihong Ye2, Weiying Zhang1, Xiaodong Zhang1

1State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China

2State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, P.R. China

Correspondence to:

Xiaodong Zhang, email: [email protected]

Weiying Zhang, email: [email protected]

Keywords: HBx, C4BP, complement attack, HCC

Received: November 24, 2015     Accepted: March 14, 2016     Published: March 30, 2016

ABSTRACT

Hepatitis B virus X protein (HBx) plays crucial roles in the development of hepatocellular carcinoma (HCC). We previously showed that HBx protected hepatoma cells from complement attack by activation of CD59. Moreover, in this study we found that HBx protected hepatoma cells from complement attack by activation of C4b-binding protein α (C4BPα), a potent inhibitor of complement system. We observed that HBx were positively correlated with those of C4BPα in clinical HCC tissues. Mechanistically, HBx activated the promoter core region of C4BPα, located at -1199/-803nt, through binding to transcription factor Sp1. In addition, chromatin immunoprecipitation (ChIP) assays showed that HBx was able to bind to the promoter of C4BPα, which could be blocked by Sp1 silencing. Functionally, knockdown of C4BPα obviously increased the deposition of C5b-9, a complex of complement membrane attack, and remarkably abolished the HBx-induced resistance of hepatoma cells from complement attack in vitro and in vivo. Thus, we conclude that HBx up-regulates C4BPα through activating transcription factor Sp1 in protection of liver cancer cells from complement attack. Our finding provides new insights into the mechanism by which HBx enhances protection of hepatoma cells from complement attack.


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