Hepatology文章：揭示宿主內(nèi)的小RNA參與乙肝病毒表達(dá)調(diào)控

Hepatology文章：揭示宿主內(nèi)的小RNA參與乙肝病毒表達(dá)調(diào)控

　　乙型肝炎病毒（hepatitis B virus，HBV）感染可引起肝臟的急性和慢性炎癥。急性感染一般表現(xiàn)為自限性肝炎，除爆發(fā)性肝炎外，對(duì)人體的危害較�。欢�慢性感染則與肝硬化（cirrhosis）和原發(fā)性肝癌（hepatocellular carcinoma，HCC）的發(fā)生密切相關(guān)。全球約有3.5億的HBV攜帶者，最終發(fā)展為肝癌的比例高達(dá)25%，每年死于HBV相關(guān)肝癌的患者高達(dá)100多萬(wàn)。中國(guó)為HBV高度流行的國(guó)家，HBV感染是嚴(yán)重危害國(guó)民健康和生活質(zhì)量的重要傳染性疾病。

　　MicroRNA 是一類小的非編碼RNA，可通過(guò)降解靶mRNA和抑制靶mRNA翻譯等方式調(diào)控基因表達(dá)，在動(dòng)植物的生長(zhǎng)發(fā)育、腫瘤的發(fā)生發(fā)展、感染性疾病的發(fā)生發(fā)展中有重要作用。近年來(lái)的研究發(fā)現(xiàn)，microRNA 參與了HCV病毒、HIV病毒、EB病毒、Plum pox病毒、CMV病毒、Kaposi''s 肉瘤相關(guān)病毒等病毒在宿主細(xì)胞內(nèi)的復(fù)制過(guò)程，調(diào)控宿主細(xì)胞與病毒的相互作用，影響疾病的發(fā)生發(fā)展及轉(zhuǎn)歸，有可能成為新的抗病毒治療靶點(diǎn)。程京教授課題組、郭永副研究員與北京大學(xué)人民醫(yī)院魏來(lái)教授、重慶醫(yī)科大學(xué)黃愛(ài)龍教授課題組合作，利用生物芯片平臺(tái)結(jié)合功能研究發(fā)現(xiàn)miR-372/373這簇小RNA可通過(guò)調(diào)控宿主細(xì)胞的轉(zhuǎn)錄因子促進(jìn)HBV表達(dá)。該研究通過(guò)將microRNA和轉(zhuǎn)錄因子這兩類細(xì)胞內(nèi)非常重要的調(diào)控因子相關(guān)聯(lián)，為HBV表達(dá)調(diào)控研究提供了新的方向，具有重要的理論意義。

　　上述研究的博奧生物晶芯®哺乳動(dòng)物miRNA芯片服務(wù)與Real time RT-PCR服務(wù)在博奧生物有限公司完成。

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.

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