乙型肝炎病毒(hepatitis B virus,HBV)感染可引起肝脏的急性和慢性炎症。急性感染一般表现为自限性肝炎,除爆发性肝炎外,对人体的危害较小;而慢性感染则与肝硬化(cirrhosis)和原发性肝癌(hepatocellular carcinoma,HCC)的发生密切相关。全球约有3.5亿的HBV携带者,最终发展为肝癌的比例高达25%,每年死于HBV相关肝癌的患者高达100多万。中国为HBV高度流行的国家,HBV感染是严重危害国民健康和生活质量的重要传染性疾病。
MicroRNA 是一类小的非编码RNA,可通过降解靶mRNA和抑制靶mRNA翻译等方式调控基因表达,在动植物的生长发育、肿瘤的发生发展、感染性疾病的发生发展中有重要作用。近年来的研究发现,microRNA 参与了HCV病毒、HIV病毒、EB病毒、Plum pox病毒、CMV病毒、Kaposi's 肉瘤相关病毒等病毒在宿主细胞内的复制过程,调控宿主细胞与病毒的相互作用,影响疾病的发生发展及转归,有可能成为新的抗病毒治疗靶点。程京教授课题组、郭永副研究员与北京大学人民医院魏来教授、重庆医科大学黄爱龙教授课题组合作,利用生物芯片平台结合功能研究发现miR-372/373这簇小RNA可通过调控宿主细胞的转录因子促进HBV表达。该研究通过将microRNA和转录因子这两类细胞内非常重要的调控因子相关联,为HBV表达调控研究提供了新的方向,具有重要的理论意义。
上述研究的博奥生物晶芯®哺乳动物miRNA芯片服务与Real time RT-PCR服务在博奥生物有限公司完成。
原文摘要:
MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B
MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of gene expression. Recent evidence has indicated the pathological relevance of miRNA dysregulation in hepatitis virus infection; however, the roles of microRNAs in the regulation of hepatitis B virus (HBV) expression are still largely unknown. In this study we identified that miR-373 was up-regulated in HBV-infected liver tissues and that the members of the miRs-371-372-373 (miRs-371-3) gene cluster were also significantly co-up-regulated in HBV-producing HepG2.2.15 cells. A positive in vivo association was identified between hepatic HBV DNA levels and the copy number variation of the miRs-371-3 gene cluster. The enhanced expression of miRs-372/373 stimulated the production of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with 1.33HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct functional target of miRs-372/373 by in silico algorithms and this was subsequently confirmed by western blotting and luciferase reporter assays. Knockdown of NFIB by small interfering RNA (siRNA) promoted HBV expression, whereas rescue of NFIB attenuated the stimulation in the 1.3xHBV-transfected HepG2 cells. Conclusion: Our study revealed that miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (NFIB). This novel model provides new insights into the molecular basis in HBV and host interaction.
原文出处:http://onlinelibrary.wiley.com/doi/10.1002/hep.24441/abstract;jsessionid=6B0DBCF4745EF5CB4D33C995287182BA.d01t04
来源于:博奥生物有限公司生物芯片北京国家工程研究中心
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