乙型肝炎病毒相关肝细胞癌的表观遗传机制

StephenW

Epigenetic mechanisms in hepatitis B virus-associated hepatocellular carcinoma
Ourania Andrisani  1
Affiliations
Affiliation

    1
    Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.

    PMID: 33614973 PMCID: PMC7894648 DOI: 10.20517/2394-5079.2020.83

Abstract

Chronic infection of the liver by the hepatitis B virus (HBV) is associated with increased risk for developing hepatocellular carcinoma (HCC). A multitude of studies have investigated the mechanism of liver cancer pathogenesis due to chronic HBV infection. Chronic inflammation, expression of specific viral proteins such as HBx, the integration site of the viral genome into the host genome, and the viral genotype, are key players contributing to HCC pathogenesis. In addition, the genetic background of the host and exposure to environmental carcinogens are also predisposing parameters in hepatocarcinogenesis. Despite the plethora of studies, the molecular mechanism of HCC pathogenesis remains incompletely understood. In this review, the focus is on epigenetic mechanisms involved in the pathogenesis of HBV-associated HCC. Epigenetic mechanisms are dynamic molecular processes that regulate gene expression without altering the host DNA, acting by modifying the host chromatin structure via covalent post-translational histone modifications, changing the DNA methylation status, expression of non-coding RNAs such as microRNAs and long noncoding RNAs, and altering the spatial, 3-D organization of the chromatin of the virus-infected cell. Herein, studies are described that provide evidence in support of deregulation of epigenetic mechanisms in the HBV-infected/-replicating hepatocyte and their contribution to hepatocyte transformation. In contrast to genetic mutations which are permanent, epigenetic alterations are dynamic and reversible. Accordingly, the identification of essential molecular epigenetic targets involved in HBV-mediated HCC pathogenesis offers the opportunity for the design and development of novel epigenetic therapeutic approaches.

Keywords: DNA methylation; Hepatitis B virus; chromatin/histone modifications; epigenetics; hepatocellular carcinoma; lncRNA; miRNA.

StephenW

乙型肝炎病毒相关肝细胞癌的表观遗传机制
Ourania Andrisani 1
隶属关系
联系

    1个
    普渡大学基本医学系和普渡大学癌症研究中心，西拉法叶，美国47907。

    PMID：33614973 PMCID：PMC7894648 DOI：10.20517 / 2394-5079.2020.83

抽象的

乙型肝炎病毒（HBV）对肝脏的慢性感染与发生肝细胞癌（HCC）的风险增加有关。大量研究调查了慢性HBV感染引起的肝癌发病机理。慢性炎症，特定病毒蛋白（例如HBx）的表达，病毒基因组整合入宿主基因组的位点以及病毒基因型是导致HCC发病的关键因素。另外，宿主的遗传背景和暴露于环境致癌物也是肝癌发生中的诱因。尽管有大量的研究，肝癌发病机理的分子机制仍然不完全了解。在这篇综述中，重点是与HBV相关HCC的发病机制有关的表观遗传机制。表观遗传机制是动态分子过程，其在不改变宿主DNA的情况下调节基因表达，通过共价翻译后组蛋白修饰来修饰宿主染色质结构，改变DNA甲基化状态，表达非编码RNA（例如微RNA和长非编码RNA）来发挥作用。 ，并改变病毒感染细胞染色质的空间3-D组织。本文中，描述了研究，这些研究提供了证据来支持乙肝病毒感染/复制肝细胞中表观遗传机制的失调及其对肝细胞转化的贡献。与永久的遗传突变相反，表观遗传改变是动态且可逆的。因此，鉴定涉及HBV介导的HCC发病机理的基本分子表观遗传学靶标为设计和开发新型表观遗传学治疗方法提供了机会。

关键词：DNA甲基化；乙型肝炎病毒;染色质/组蛋白修饰表观遗传学肝细胞癌； lncRNA; miRNA。

StephenW

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