Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, China.
Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, 646000, China.
Hepatol Int. 2022 Aug;16(4):741-754. doi: 10.1007/s12072-022-10351-6. Epub 2022 Jun 1.
Chronic hepatitis B virus (HBV) infection is a worldwide health problem. Hepatitis B virus X protein (HBx), a pleiotropic regulatory protein encoded by HBV, is necessary for the transcription of HBV covalently closed circular DNA (cccDNA) minichromosomes, and affects the epigenetic regulation of host cells. The epigenetic reprogramming of HBx on host cell genome is strongly involved in HBV-related HCC carcinogenesis. Here, we review the latest findings of the epigenetic regulation induced by HBx protein in hepatocellular carcinoma (HCC), including DNA methylation, histone modification and non-coding RNA expression. The influence of HBx on the epigenetic regulation of cccDNA is also summarized. In addition, preliminary studies of targeted drugs for epigenetic changes induced by HBx are also discussed. The exploration of epigenetic markers as potential targets will help to develop new prevention and/or treatment methods for HBx-related HCC.
慢性乙型肝炎病毒（HBV）感染是一个全球性的健康问题。乙型肝炎病毒 X 蛋白（HBx）是 HBV 编码的一种多功能调节蛋白，是 HBV 共价闭合环状 DNA（cccDNA）微染色体转录所必需的，并且影响宿主细胞的表观遗传调控。HBx 对宿主细胞基因组的表观遗传重编程强烈参与 HBV 相关 HCC 的致癌发生。在这里，我们综述了 HBx 蛋白在肝细胞癌（HCC）中诱导的表观遗传调控的最新发现，包括 DNA 甲基化、组蛋白修饰和非编码 RNA 的表达。还总结了 HBx 对 cccDNA 表观遗传调控的影响。此外，还讨论了针对 HBx 诱导的表观遗传变化的靶向药物的初步研究。作为潜在靶点的表观遗传标志物的探索将有助于开发针对 HBx 相关 HCC 的新的预防和/或治疗方法。
