Tian Yongjun, Ou Jing-hsiung James
Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, 90033, USA.
Virol Sin. 2015 Apr;30(2):85-91. doi: 10.1007/s12250-015-3582-7. Epub 2015 Apr 7.
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Its chronic infection can lead to chronic liver inflammation and the accumulation of genetic alterations to result in the oncogenic transformation of hepatocytes. HBV can also sensitize hepatocytes to oncogenic transformation by causing genetic and epigenetic changes of the host chromosomes. HBV DNA can insert into host chromosomes and recent large-scale whole-genome sequencing studies revealed recurrent HBV DNA integrations sites that may play important roles in the initiation of hepatocellular carcinogenesis. HBV can also cause epigenetic changes by altering the methylation status of cellular DNA, the post-translational modification of histones, and the expression of microRNAs. These changes can also lead to the eventual hepatocellular transformation. These recent findings on the genetic and epigenetic alterations of the host chromosomes induced by HBV opened a new avenue for the development of novel diagnosis and treatments for HBV-induced HCC.
乙型肝炎病毒(HBV)是肝细胞癌(HCC)的主要病因。其慢性感染可导致慢性肝脏炎症以及基因改变的积累,从而导致肝细胞发生致癌转化。HBV还可通过引起宿主染色体的基因和表观遗传变化,使肝细胞对致癌转化敏感。HBV DNA可插入宿主染色体,最近的大规模全基因组测序研究揭示了反复出现的HBV DNA整合位点,这些位点可能在肝细胞癌发生的起始过程中发挥重要作用。HBV还可通过改变细胞DNA的甲基化状态、组蛋白的翻译后修饰以及微小RNA的表达引起表观遗传变化。这些变化也可导致最终的肝细胞转化。关于HBV诱导的宿主染色体基因和表观遗传改变的这些最新发现,为开发针对HBV诱导的HCC的新型诊断和治疗方法开辟了一条新途径。