title: Hepatitis B virus X protein up-regulates C4b-binding protein α through activating transcription factor Sp1 in protection of hepatoma cells from complement attack.
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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Minying
authors.initials: M
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D050716:Complement C4b-Binding Protein / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C055609:C4BPA protein, human; D050716:Complement C4b-Binding Protein; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: C4BP; HBx; HCC; complement attack