乙型肝炎病毒X蛋白的研究進展_《華西醫學》

作者：

龔道銀 ¹ , 陳恩強 ² , 朱柯霓 ³ , 張冬雪 ¹ , 俞尤嘉 ¹ ,  黃飛駿 ¹

1 四川大學華西基礎醫學與法醫學院（成都，610041）;2四川大學華西醫院感染性疾病中心;3武警四川總隊成都醫院;

關鍵詞：

X蛋白乙型肝炎病毒復制肝細胞癌

DOI：

10.7507/1002-0179.20130194

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

乙型肝炎病毒(HBV)慢性持續感染與肝細胞癌（HCC）的發生密切相關。由HBV X基因編碼的X蛋白（HBx）是一個多功能蛋白，可通過反式激活和蛋白相互作用持續調控病毒的生活周期和宿主細胞的代謝，最終導致肝細胞癌變。因此，近年來對于HBx在病毒復制和致HCC中的作用機制成為研究熱點。

引用本文： 龔道銀,陳恩強,朱柯霓,張冬雪,俞尤嘉,黃飛駿. 乙型肝炎病毒X蛋白的研究進展. 華西醫學, 2013, 28(4): 609-613. doi: 10.7507/1002-0179.20130194 復制

1.	Ng SA, Lee C. Hepatitis Bvirus X gene and hepatocarcinogenesis[J]. J Gastroenterol, 2011, 46(8): 974-990.
2.	Koike K. Hepatitis B virus X gene is implicated in liver carcinogenesis[J]. Cancer Lett, 2009, 286(1): 60-68.
3.	Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis[J]. J Hepatol, 2010, 52(4): 594-604.
4.	王月賓, 唐紅. 乙型肝炎病毒X蛋白在HBV復制中作用的研究進展[J]. 華西醫學, 2008, 23 (4): 917-918.
5.	Tang H, Oishin, Kanekos, et al. Molecular functions and biological roles of hepatitis B virus x protein[J]. Cancer Sci, 2006, 97(10): 977-983.
6.	Maria Stella De Mitri, Romina Cassini, Mauro Bernardi. Hepatitis Bvirus-related hepatocarcinogenesis: Molecular oncogenic potential of clear or occult infections[J]. Eur J Cancer, 2010, 46(12): 2178-2186.
7.	Chau DK f, Chen G G, Zhang H, et al. Differential Functions of C-and N-Terminal Hepatitis B x Protein in Liver Cells Treated with Doxorubicinin Normoxicor Hypoxic Condition[J]. PLoS ONE, 2012, 7(11): 50118.
8.	Bouchard MJ, Schneider RJ. The enigmatic X gene of hepatitis B virus[J]. J Virol, 2004, 78 (23): 12725 - 12734.
9.	Bouchard MJ, Navas-Martin S. Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges[J]. Cancer Lett, 2011, 305(2): 123-143.
10.	Tang H, Delgermaa L, Huang FJ, et al. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication[J]. J Virol, 2005, 79(9): 5548-5556.
11.	MAA van de Klundert, FJ. vanHemert, HL Zaaijer. The Hepatitis B virus X protein inhibits thymine DNA glycosylase initiated base excision repair[J]. Plos One, 2012, 7(11): 48940.
12.	Rawat S, Clippinger AJ, Bouchard MJ. Modulation of Apoptotic Signaling by the Hepatitis B Virus X Protein[J]. Viruses, 2012, 4: 2945-2972.
13.	Zhang Tao, Zhang Jp, You Xn, 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.
14.	Du Y, Kong G, You X, et al. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18[J]. J Biol Chem, 2012, 287(31): 26302-26311.
15.	Clippinger AJ, Bouchard MJ. Hepatitis B virus HBx protein localizes to mitochondria in primary rat hepatocytes and modulates mitochondrial membrane potential[J]. J Virol, 2008, 82(14): 6798-6811.
16.	Knoll S, Fürst K, Thomas S, et al. Dissection of cell context-dependent interactions between HBx and p53 family members in regulation of apoptosis: a role for HBV-induced HCC[J]. Cell Cycle, 2011, 10(20): 3554-3565.
17.	Gearhart TL, Bouchard MJ. The hepatitis B virus X protein modulates hepatocyte proliferation pathways to stimulate viral replication[J]. J Virol, 2010, 84(6): 2675-2686.
18.	Wang Fan, Xia XM, Wang JL, et al. Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells[J]. Biotechnol Lett, 2013, 35(1): 29-37.
19.	TM Bui-Nguyen, SB Pakala, RD Sirigiri.NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx[J]. Oncogene, 2010, 29(8): 1179-1189.
20.	Zhang ZS, Sun E, James JH, et al. Inhibition of Cellular Proteasome activities mediates HBx-independent hepatitis B virus replication in vivo[J]. J Virol, 2010, 84(18): 9326-9331.
21.	S Kim, S-Y Park, H Yong, et al. HBV X protein targets hBubR1, which induces dysregulation of the mitotic Checkpoint[J]. Oncogene, 2008, 27(24): 3457-3464.
22.	Wei W, Huang W, Pan Y, et al. Functional switch of viral protein HBx on cell apoptosis, transformation, and tumorigenesis in association with oncoprotein Ras[J]. Cancer Lett, 2006, 244(1): 119-128.
23.	Belloni L, Pollici no T, De Nicola F, et al. Nuclear HBx binds the HBV mini chromosome and modifies the epigenetic regulation of cccDNA function[J]. Proc Natl Acad Sci USA, 2009, 106(47): 19975 -19979.
24.	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.
25.	Ye Jin Kim, Jin Kyu Jung, Sun Young Lee, et al. Hepatitis B virus X protein overcomes stress-induced premature senescence by repressing p16INK4α expression via DNA methylation[J]. Cancer Lett, 2010, 288(2): 226-235.
26.	Michael C Kew. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma[J]. J Gastroen Hepatol, 2011, 26 (Suppl 1): 144-152.
27.	Wen W, Ding J, Sun W, et al. Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression[J]. Hepatology, 2012, 55(6): 1787-1798.
28.	Wei Xf, Xiang TX, Ren GS, et al. miR-101 is sdown-regulated by the hepatitis B virus x protein and induces aberrant DNA methylation by targeting DNA methyltransferase 3A[J]. Cell Signal, 2013, 25(2): 439-446.
29.	Wang Peng, Guo QS, Wang ZW, et al. HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway[J]. Mol Cell Biochem, 2013, 372(1-2): 161-168.

1. 　Ng SA, Lee C. Hepatitis Bvirus X gene and hepatocarcinogenesis[J]. J Gastroenterol, 2011, 46(8): 974-990.
2. 　Koike K. Hepatitis B virus X gene is implicated in liver carcinogenesis[J]. Cancer Lett, 2009, 286(1): 60-68.
3. 　Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis[J]. J Hepatol, 2010, 52(4): 594-604.
4. 　王月賓, 唐紅. 乙型肝炎病毒X蛋白在HBV復制中作用的研究進展[J]. 華西醫學, 2008, 23 (4): 917-918.
5. 　Tang H, Oishin, Kanekos, et al. Molecular functions and biological roles of hepatitis B virus x protein[J]. Cancer Sci, 2006, 97(10): 977-983.
6. 　Maria Stella De Mitri, Romina Cassini, Mauro Bernardi. Hepatitis Bvirus-related hepatocarcinogenesis: Molecular oncogenic potential of clear or occult infections[J]. Eur J Cancer, 2010, 46(12): 2178-2186.
7. 　Chau DK f, Chen G G, Zhang H, et al. Differential Functions of C-and N-Terminal Hepatitis B x Protein in Liver Cells Treated with Doxorubicinin Normoxicor Hypoxic Condition[J]. PLoS ONE, 2012, 7(11): 50118.
8. 　Bouchard MJ, Schneider RJ. The enigmatic X gene of hepatitis B virus[J]. J Virol, 2004, 78 (23): 12725 - 12734.
9. 　Bouchard MJ, Navas-Martin S. Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges[J]. Cancer Lett, 2011, 305(2): 123-143.
10. 　Tang H, Delgermaa L, Huang FJ, et al. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication[J]. J Virol, 2005, 79(9): 5548-5556.
11. 　MAA van de Klundert, FJ. vanHemert, HL Zaaijer. The Hepatitis B virus X protein inhibits thymine DNA glycosylase initiated base excision repair[J]. Plos One, 2012, 7(11): 48940.
12. 　Rawat S, Clippinger AJ, Bouchard MJ. Modulation of Apoptotic Signaling by the Hepatitis B Virus X Protein[J]. Viruses, 2012, 4: 2945-2972.
13. 　Zhang Tao, Zhang Jp, You Xn, 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.
14. 　Du Y, Kong G, You X, et al. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18[J]. J Biol Chem, 2012, 287(31): 26302-26311.
15. 　Clippinger AJ, Bouchard MJ. Hepatitis B virus HBx protein localizes to mitochondria in primary rat hepatocytes and modulates mitochondrial membrane potential[J]. J Virol, 2008, 82(14): 6798-6811.
16. 　Knoll S, Fürst K, Thomas S, et al. Dissection of cell context-dependent interactions between HBx and p53 family members in regulation of apoptosis: a role for HBV-induced HCC[J]. Cell Cycle, 2011, 10(20): 3554-3565.
17. 　Gearhart TL, Bouchard MJ. The hepatitis B virus X protein modulates hepatocyte proliferation pathways to stimulate viral replication[J]. J Virol, 2010, 84(6): 2675-2686.
18. 　Wang Fan, Xia XM, Wang JL, et al. Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells[J]. Biotechnol Lett, 2013, 35(1): 29-37.
19. 　TM Bui-Nguyen, SB Pakala, RD Sirigiri.NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx[J]. Oncogene, 2010, 29(8): 1179-1189.
20. 　Zhang ZS, Sun E, James JH, et al. Inhibition of Cellular Proteasome activities mediates HBx-independent hepatitis B virus replication in vivo[J]. J Virol, 2010, 84(18): 9326-9331.
21. 　S Kim, S-Y Park, H Yong, et al. HBV X protein targets hBubR1, which induces dysregulation of the mitotic Checkpoint[J]. Oncogene, 2008, 27(24): 3457-3464.
22. 　Wei W, Huang W, Pan Y, et al. Functional switch of viral protein HBx on cell apoptosis, transformation, and tumorigenesis in association with oncoprotein Ras[J]. Cancer Lett, 2006, 244(1): 119-128.
23. 　Belloni L, Pollici no T, De Nicola F, et al. Nuclear HBx binds the HBV mini chromosome and modifies the epigenetic regulation of cccDNA function[J]. Proc Natl Acad Sci USA, 2009, 106(47): 19975 -19979.
24. 　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.
25. 　Ye Jin Kim, Jin Kyu Jung, Sun Young Lee, et al. Hepatitis B virus X protein overcomes stress-induced premature senescence by repressing p16INK4α expression via DNA methylation[J]. Cancer Lett, 2010, 288(2): 226-235.
26. 　Michael C Kew. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma[J]. J Gastroen Hepatol, 2011, 26 (Suppl 1): 144-152.
27. 　Wen W, Ding J, Sun W, et al. Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression[J]. Hepatology, 2012, 55(6): 1787-1798.
28. 　Wei Xf, Xiang TX, Ren GS, et al. miR-101 is sdown-regulated by the hepatitis B virus x protein and induces aberrant DNA methylation by targeting DNA methyltransferase 3A[J]. Cell Signal, 2013, 25(2): 439-446.
29. 　Wang Peng, Guo QS, Wang ZW, et al. HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway[J]. Mol Cell Biochem, 2013, 372(1-2): 161-168.

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