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浙江大学学报（医学版）
浙江大学学报（医学版）  2021, Vol. 50 Issue (1): 113-122    DOI: 10.3724/zdxbyxb-2021-0032
综述     
乙型肝炎病毒诱发肝细胞癌分子机制研究进展
邵一鸣1,2(),苏力德1,2,郝睿1,2,王茜茜2,那仁满都拉1,2,*()
1. 内蒙古医科大学药学院，内蒙古 呼和浩特 010000
2. 浙江大学医学院，浙江 杭州 310058
Advances on molecular mechanism of hepatitis B virus-induced hepatocellular carcinoma
SHAO Yiming1,2(),SU Lide1,2,HAO Rui1,2,WANG Qianqian2,NARANMANDURA Hua1,2,*()
1. College of Pharmaceutical Sciences，Inner Mongolia Medical University，Hohhot 010000，China; 2. School of Medicine，Zhejiang University，Hangzhou 310058，China
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摘要：

乙型肝炎病毒（HBV）诱导肝细胞癌（HCC）的发生是一个多阶段、多因素相互作用的复杂过程。HBV促进HCC发生、发展的途径主要包括HBV DNA整合至宿主肝细胞基因组从而影响整合位点的基因功能、形成致癌作用的截短蛋白、造成宿主基因组的不稳定，HBV基因组S、C、X区基因突变，HBV X基因编码的HBx蛋白激活原癌基因、抑制抑癌基因等。本文综述了近年来HBV诱发HCC分子机制的研究进展，以期为HCC预防、早期预测及术后辅助治疗提供理论指导。
关键词： 乙型肝炎病毒;  肝细胞癌;  基因突变;  基因整合;  乙型肝炎病毒X蛋白;  综述    
Abstract:

The pathogenesis of hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC） is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site，resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S，C，and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes，leading to the HCC occurrence. In this article，the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed，so as to provide insights into the prevention，early prediction and postoperative adjuvant therapy of HCC.
Key words: Hepatitis B virus    Hepatocellular carcinoma    Gene mutation    Gene integration    Hepatitis B virus X protein    Review
收稿日期: 2020-09-23 出版日期: 2021-05-14
CLC:  R735.7  
基金资助: 国家自然科学基金（82003875，81872942）; 浙江省卫生高层次创新人才培养工程[浙卫发（2018）62号]; 浙江省博士后择优（ZJ2020154）
通讯作者: 那仁满都拉     E-mail: 2018120006@stu.immu.edu.cn;narenman@zju.edu.cn
作者简介: 邵一鸣，硕士研究生，主要从事急性髓细胞白血病的机制研究; E-mail:2018120006@stu.immu.edu.cn; https://orcid.org/0000-0001-9594-3738
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邵一鸣,苏力德,郝睿,王茜茜,那仁满都拉. 乙型肝炎病毒诱发肝细胞癌分子机制研究进展[J]. 浙江大学学报（医学版）, 2021, 50(1): 113-122.

SHAO Yiming,SU Lide,HAO Rui,WANG Qianqian,NARANMANDURA Hua. Advances on molecular mechanism of hepatitis B virus-induced hepatocellular carcinoma. J Zhejiang Univ (Med Sci), 2021, 50(1): 113-122.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0032    或    http://www.zjujournals.com/med/CN/Y2021/V50/I1/113

图 1  乙型肝炎病毒诱发肝细胞癌的示意图 乙型肝炎病毒（HBV） DNA通过整合至宿主基因组中、HBV基因组突变以及乙型肝炎病毒 X蛋白（HBx）等途径促进肝细胞癌（HCC）的发生和发展.APOBEC3：载脂蛋白B mRNA编辑酶催化多肽家族3.
图 2  乙型肝炎病毒基因组结构示意图 A：乙型肝炎病毒（HBV）基因组结构为部分双链环状DNA，包含4个主要的开放阅读框，分别为S区、C区、P区、X区.B：S区基因分为前S1区（nt2848~3204）、前S2区（nt3205~154）和S区（nt155~835），其中S基因编码的乙型肝炎表面抗原是HBV感染的标志物；P区基因覆盖了3/4的基因组，其主要编码DNA聚合酶；C区包括前C区基因（nt1814~1900）和C区基因（nt1901~2452），分别编码乙型肝炎e抗原和乙型肝炎核心抗原；X区基因（nt1374~1838）编码产物是含154aa的X蛋白，该蛋白可通过多种机制在HBV致肝细胞癌过程中起重要作用.
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