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乙型肝炎病毒X蛋白在原发性肝癌中的作用

廖凯 张雷达

引用本文:
Citation:

乙型肝炎病毒X蛋白在原发性肝癌中的作用

DOI: 10.3969/j.issn.1001-5256.2014.01.023
基金项目: 

国家自然科学基金资助项目(81071979); 

详细信息
  • 中图分类号: R735.7

Role of hepatitis B virus X protein in development and progression of primary liver cancer

Research funding: 

 

  • 摘要: 乙型肝炎病毒X蛋白(HBx)是一种由HBV X基因编码的多功能蛋白,参与调节基因转录、细胞信号转导、细胞增殖转化、细胞周期和细胞凋亡。目前HBx蛋白被认为在HBV诱发原发性肝癌的过程中发挥重要作用。介绍了HBx蛋白与癌基因、抑癌基因、细胞增殖、细胞凋亡、肝癌侵袭转移和肝癌干细胞的关系,探讨了HBx蛋白在肝癌发生发展中的作用。

     

  • [1]MISRAL KP, MUKHERJI A, KUMAR V.The conserved aminoterminal region (amino acids 1-20) of the hepatitis B virus X protein shows a transrepression function[J].Virus Res, 2004, 105 (2) :157-165.
    [2] NIJHARA R, JANA SS, GOSWAMI SK, et al.Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo[J].J Virol, 2001, 75 (21) :10348-10358.
    [3] HWANG GY, LIN CY, HUANG LM, et al.Detection of the hepatitis B virus X protein (HBx) antigen and anti-HBx antibodies in cases of human hepatocellular carcinoma[J].J Clin Microbiol, 2003, 41 (12) :5598-5603.
    [4]CHEN GG, LI MY, HO RL, et al.Identification of hepatitis B virus X gene mutation in Hong Kong patients with hepatocellular carcinoma[J].J Clin Virol, 2005, 34 (1) :7-12.
    [5] TOH ST, JIN Y, LIU L, et al.Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations[J].Carcinogenesis, 2013, 34 (4) :787-798.
    [6] ZHANG H, SHAN CL, LI N, et al.Identification of a natural mutant of HBV X protein truncated 27 amino acids at the COOH terminal and its effect on liver cell proliferation[J].Acta Pharmacol Sin, 2008, 29 (4) :473-480.
    [7]ZHANG X, YOU X, LI N, et al.Involvement of hepatitis B virus X gene (HBx) integration in hepatocarcinogenesis via a recombination of HBx/Alu core sequence/subtelomeric DNA[J].FEBS Lett, 2012, 586 (19) :3215-3221.
    [8] KWUN HJ, JANG KL.Natural variants of hepatitis B virus X protein have differential effects on the expression of cyclin-dependent kinase inhibitor p21 gene[J].Nucleic Acids Res, 2004, 32 (7) :2202-2213.
    [9]KLEIN NP, SCHNEIDER RJ.Activation of Src family kinases by hepatitis B virus HBx protein and coupled signaling to Ras[J].Mol Cell Biol, 1997, 17 (11) :6427-6436.
    [10]KALRA N, KUMAR V.The X protein of hepatitis B virus binds to the F box protein Skp2 and inhibits the ubiquitination and proteasomal degradation of c-myc[J].FEBS Lett, 2006, 580 (2) :431-436.
    [11] ZHANG T, ZHANG J, YOU X, et al.Hepatitis B virus X protein modulates oncogene Yes-associated protein by CREB to promote growth of hepatoma cells[J].Hepatology, 2012, 56 (6) :2051-2059.
    [12]TU H, BONURA C, GIANNINI C, et al.Biological impact of natural COOH-terminal deletions of hepatitis B virus X protein in hepatocellular carcinoma tissues[J].Cancer Res, 2001, 61 (21) :7803-7810.
    [13]CHEN J, YANG LM, CUI B, et al.Expression and significance of HBx, Survivin and P53 protein in human hepatocellular carcinoma[J].China Med Herald, 2012, 9 (7) :30-32. (in Chinese) 陈江, 杨柳明, 崔彬, 等.HBx、Survivin及P53在肝细胞癌中的表达及意义[J].中国医药导报, 2012, 9 (7) :30-32.
    [14]LEE SG, RHO HM.Transcriptional repression of the human p53gene by hepatitis B viral X protein[J].Oncogene, 2000, 19 (3) :468-471.
    [15]YANO M, OHKOSHI S, AOKI YH, et al.Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression[J].Liver Int, 2013.doi: 10.1111/liv.12176.
    [16]WANG ZW, PENG ZH, LI K, et al.Role of P16 in pathogenesis of HBV-related hepatocellular carcinoma[J].Chin J Oncol, 2003, 25 (4) :356-358. (in Chinese) 王兆文, 彭志海, 李克, 等.P16影响乙肝病毒相关性肝细胞肝癌的发生[J].中华肿瘤杂志, 2003, 25 (4) :356-358.
    [17]ZHANG X, DONG N, ZHANG H, et al.Effects of hepatitis B virus X protein on human telomerase reverse transcriptase expression and activity in hepatoma cells[J].J Lab Clin Med, 2005, 145 (2) :98-104.
    [18]WANG F, ZHOU H, XIA X, et al.Activated Notch signaling is required for hepatitis B virus X protein to promote proliferation and survival of human hepatic cells[J].Cancer Lett, 2010, 298 (1) :64-73.
    [19]WANG F, XIA X, WANG J, et al.Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells[J].Biotechnol Lett, 2013, 35 (1) :29-37.
    [20]WANG F, ZHOU H, YANG Y, et al.Hepatitis B virus X protein promotes the growth of hepatocellular carcinoma by modulation of the Notch signaling pathway[J].Oncol Rep, 2012, 27 (4) :1170-1176.
    [21] YEN CJ, LIN YJ, YEN CS, et al.Hepatitis B virus X protein upregulates mTOR signaling through IKKβto increase cell proliferation and VEGF production in hepatocellular carcinoma[J].PLoS One, 2012, 7 (7) :e41931.
    [22]YOO YG, LEE MO.Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor[J].J Biol Chem, 2004, 279 (35) :36242-36249.
    [23]KUO CY, CHOU TY, CHEN CM, et al.Hepatitis B virus X protein disrupts stress fiber formation and triggers apoptosis[J].Virus Res, 2013.doi: 10.1016/j.virusres.2013.03.017.
    [24]KIM SY, KIM JK, KIM HJ, et al.Hepatitis B virus X protein sensitizes UV-induced apoptosis by transcriptional transactivation of Fas ligand gene expression[J].IUBMB Life, 2005, 57 (9) :651-658.
    [25]CHENG AS, YU J, LAI PB, et al.COX-2 mediates hepatitis B virus X protein abrogation of p53-induced apoptosis[J].Biochem Biophys Res Commun, 2008, 374 (2) :175-180.
    [26]KUO TC, CHAO CC.Hepatitis B virus X protein prevents apoptosis of hepatocellular carcinoma cells by upregulating SATB1 and HURP expression[J].Biochem Pharmacol, 2010, 80 (7) :1093-1102.
    [27]KIM HJ, KIM SY, KIM J, et al.Hepatitis B virus X protein induces apoptosis by enhancing translocation of Bax to mitochondria[J].IUBMB Life, 2008, 60 (7) :473-480.
    [28]TERRADILLOS O, de LA COSTE A, POLLICINO T, et al.The hepatitis B virus X protein abrogates Bcl-2-mediated protection against Fas apoptosis in the liver[J].Oncogene, 2002, 21 (3) :377-386.
    [29]WANG JY, WANG YC, WANG L, et al.Effects of salinomycin on proliferative, invasive and metastatic abilities of hepatoma cell line HepG2 in vitro[J].Chin J Cell Biol, 2013, 35 (5) :655-660. (in Chinese) 王晶宇, 王一辰, 王丽, 等.盐霉素对肝癌HepG2细胞体外增殖和侵袭转移能力的影响[J].中国细胞生物学学报, 2013, 35 (5) :655-660.
    [30]YU FL, LIU HJ, LEE JW, et al.Hepatitis B virus X protein promotes cell migration by inducing matrix metalloproteinase—3[J].J Hepatol, 2005, 42 (4) :520-527.
    [31]TANG R, KONG F, HU L, et al.Role of hepatitis B virus X protein in regulating LIM and SH3 protein 1 (LASP-1) expression to mediate proliferation and migration of hepatoma cells[J].Virol J, 2012, 9:163.
    [32]YANG SZ, ZHANG LD, ZHANG Y, et al.HBx protein induces EMT through c-Src activation in SMMC-7721 hepatoma cell line[J].Biochem Biophys Res Commun, 2009, 382 (3) :555-560.
    [33]LIU H, XU L, HE H, et al.Hepatitis B virus X protein promotes hepatoma cell invasion and metastasis by stabilizing Snail protein[J].Cancer Sci, 2012, 103 (12) :2072-2081.
    [34]YOO YG, CHO S, PARK S, et al.The carboxy terminus of the hepatitis B virus X protein is necessary and sufficient for the activation of hypoxia-inducible factor-1alpha[J].FEBS Lett, 2004, 577 (1-2) :121-126.
    [35]HUANG J, SHEN L, LU Y, et al.Parallel induction of cell proliferation and inhibition of cell differentiation in hepatic progenitor cells by hepatitis B virus X gene[J].Int J Mol Med, 2012, 30 (4) :842-848.
    [36]LI CH, WANG YJ, DONG W, et al.Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo[J].Cancer Lett, 2011, 311 (1) :1-10.
    [37]ARZUMANYAN A, FRIEDMAN T, NG IO, et al.Does the hepatitis B antigen HBx promote the appearance of liver CSCs[J].Cancer Res, 2011, 71 (10) :3701-3708.
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  • 收稿日期:  2013-04-18
  • 出版日期:  2014-01-20
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