title: Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues.
abstract: The hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). The relationship was examined between HBV antigens and IAP (inhibitor of apoptosis) family in development of HCC. The expression levels of HBV antigens (HBsAg, HBcAg, and HBxAg) and members of the IAP family (survivin, XIAP, cIAP-1, and cIAP-2) were detected immunohistochemically in tissues from 34 cases of HCC and 30 cases of liver cirrhosis. The positive rate of survivin was higher than these three molecules in all three tissue types (P < 0.05). The positive rates of HBxAg and survivin were high in HCC (76.5% and 88.2%), paratumor (85.3% and 91.2%), and liver cirrhosis (100% and 93.3%) tissues, with no significant differences between the survivin- and HBxAg-positive rates (each P > 0.05). To examine the effect of HBx on survivin expression, plasmid pCMV-X (encoding the HBx gene) was transfected transiently with or without plasmid pcDNA3-sur (encoding the survivin gene) into H7402 hepatoma cells and L-O2 human normal liver cells. Cells over-expressing HBx alone showed increased apoptosis along with a dose-dependent increase in survivin levels. However, co-expression of survivin inhibited the HBx-induced apoptosis. To examine the effect of HBx on survivin in hepatoma cells without apoptosis, plasmid pCMV-X was transfected stably into human hepatoma H7402 cells and L-O2 cells. These H7402-X and L-O2-X cells showed high-level expression of both HBx and survivin, but did not show apoptosis. The addition of pSilencer 3.0-X, an RNAi vector targeting the HBx gene, reduced the expression levels of survivin protein in H7402-X cells. Collectively, these data demonstrate that HBx upregulates survivin expression in hepatoma tissues, suggesting that HBx and survivin may both be involved in carcinogenesis of HCC.
authors.affiliation: Department of Cancer Research, Institute for Molecular Biology, Tianjin Key Laboratory of Microbial Functional Genomics, College of Life Sciences, Nankai University, Tianjin, P.R. China. zhangxd@nankai.edu.cn
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Dong
authors.forename: Lihui
authors.initials: L
authors.lastname: Yin
authors.forename: Na
authors.initials: N
authors.lastname: Cai
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ma
authors.forename: Jiacong
authors.initials: J
authors.lastname: You
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.forename: Honghui
authors.initials: H
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: He
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000077022:Survivin; D015534:Trans-Activators / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein