Kumar Ajit
George Washington University, Department of Biochemistry and Molecular Biology, Washington, DC, USA.
Biochim Biophys Acta. 2011 Nov-Dec;1809(11-12):694-9. doi: 10.1016/j.bbagrm.2011.07.010. Epub 2011 Jul 29.
In the more than two-decades since hepatitis C virus (HCV) was identified, there has been considerable improvement in our understanding of virus life cycle due largely to the development of in vitro culture systems for virus replication. Still challenges remain: HCV infection is a major risk factor for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide; yet mechanistic details of HCV infection-associated hepatocarcinogenesis remain incompletely understood. A protective vaccine is not yet available, and current therapeutic options result in sustained virus clearance only in a subset of patients. Recent interest has focused on small non-protein coding RNAs, microRNAs (miRNAs), the dependence of virus replication on miRNAs, and miRNA-regulated genes in liver cancer. Functional analysis of the miRNA-targeted genes in liver cancer has advanced our understanding of the "oncomiRs" and their role in hepatocarcinogenesis. This review focuses on the dependence of HCV replication on miRNA and role of miRNA-targeted tumor suppressor genes as molecular markers of and possible targets for developing oncomiR-targeted therapy of chronic hepatitis and HCC. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation.
自丙型肝炎病毒(HCV)被发现的二十多年来,我们对病毒生命周期的理解有了显著进步,这很大程度上归功于用于病毒复制的体外培养系统的发展。然而,挑战依然存在:在全球范围内,HCV感染是慢性肝炎、肝硬化和肝细胞癌的主要危险因素;然而,与HCV感染相关的肝癌发生的机制细节仍未完全了解。目前尚无保护性疫苗,且现有的治疗方案仅能使一部分患者实现病毒的持续清除。最近人们的兴趣集中在小型非蛋白质编码RNA、微小RNA(miRNA)、病毒复制对miRNA 的依赖性以及肝癌中受miRNA调控的基因。对肝癌中miRNA靶向基因进行功能分析,增进了我们对“致癌miRNA”及其在肝癌发生中作用 的理解。本综述重点关注HCV复制对miRNA的依赖性以及miRNA靶向肿瘤抑制基因作为慢性肝炎和肝癌致癌miRNA靶向治疗的分子标志物和可能靶点的作用。本文是名为《病毒基因调控中的微小RNA》特刊的一部分。