Tan Xiaoqing, Xun Linting, Yin Qi, Chen Chaohui, Zhang Tao, Shen Tao
Medical School, Kunming University of Science and Technology, Kunming, People's Republic of China.
Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People's Hospital of Yunnan Province, Kunming, Peoples republic of China, China.
J Viral Hepat. 2025 Feb;32(2):e14044. doi: 10.1111/jvh.14044.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatitis B virus (HBV) is the main pathogen for HCC development. HBV covalently closed circular DNA (cccDNA) forms extra-host chromatin-like minichromosomes in the nucleus of hepatocytes with host histones, non-histones, HBV X protein (HBx) and HBV core protein (HBc). Epigenetic alterations are dynamic and reversible, which regulate gene expression without altering the DNA sequence and play a pivotal role in the regulation of HCC onset and progression. The aim of this review is to elucidate the deregulation of epigenetic mechanisms involved in the pathogenesis of HBV-related HCC (HBV-HCC), including post-translational histone and non-histone modifications, DNA hypermethylation and hypomethylation, non-coding RNA modification on HBV cccDNA minichromosomes and host factors, effecting the replication/transcription of HBV cccDNA and transcription/translation of host genes, and thus HBV-HCC progression. It is expected that the epigenetic regulation perspective provides new ways for more in-depth development of therapeutic control of HBV-HCC.
肝细胞癌（HCC）是最常见的原发性肝癌。乙型肝炎病毒（HBV）是HCC发生发展的主要病原体。HBV共价闭合环状DNA（cccDNA）与宿主组蛋白、非组蛋白、HBV X蛋白（HBx）和HBV核心蛋白（HBc）一起在肝细胞的细胞核中形成类似宿主染色质的微型染色体。表观遗传改变是动态且可逆的，其在不改变DNA序列的情况下调节基因表达，并在HCC的发生和发展调控中起关键作用。本综述的目的是阐明与HBV相关的HCC（HBV-HCC）发病机制中涉及的表观遗传机制失调，包括翻译后组蛋白和非组蛋白修饰、DNA高甲基化和低甲基化、HBV cccDNA微型染色体和宿主因子上的非编码RNA修饰，这些修饰影响HBV cccDNA的复制/转录以及宿主基因的转录/翻译，进而影响HBV-HCC的进展。期望从表观遗传调控角度为更深入开展HBV-HCC的治疗控制提供新途径。
