Laboratoire de Virologie, Département de Biologie des Agents Infectieux, CHU Angers, F-49000 Angers, France.
HIFIH Laboratory UPRES EA3859, SFR ICAT 4208, Angers University, F-49000 Angers, France.
Int J Mol Sci. 2021 Dec 20;22(24):13651. doi: 10.3390/ijms222413651.
Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC.
慢性乙型肝炎病毒（HBV）感染是与肝细胞癌（HCC）最相关的常见因素之一，HCC 是全球所有癌症中第六种最常见的癌症。然而，HBV 介导的肝癌发生的发病机制尚不清楚。目前的证据表明，HBV 核心蛋白（HBc）在 HCC 的发展中可能发挥作用，如 HBV X 蛋白。核心蛋白是病毒核衣壳的结构成分，几乎参与 HBV 生命周期的每个阶段，并在 HBV 复制和发病机制中具有多种作用。最近的研究表明，HBc 能够破坏参与肝癌发生的各种途径：涉及肝癌细胞迁移和增殖的信号通路、凋亡途径以及诱导 HCC 发生的细胞代谢途径；以及免疫系统，通过表达和产生促炎细胞因子。此外，HBc 可以通过与启动子区域结合来破坏人宿主基因的表达，从而调节肝细胞的正常功能。该 HBV 蛋白还通过表观遗传改变，如 microRNA，促进 HCC 转移。这篇综述重点介绍了 HBc 蛋白在 HBV 诱导的 HCC 中的分子发病机制。
