let-7f及家族成员参与调控乙型肝炎病毒复制的研究

项目名称： let-7f及家族成员参与调控乙型肝炎病毒复制的研究

项目编号： No.81201278

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 张小楠

作者单位： 复旦大学

项目金额： 23万元

中文摘要： microRNA作为一类重要的非编码小RNA在病毒与宿主相互拮抗过程中起到了非常重要的作用。尽管目前已有一些miRNA调控乙肝病毒（HBV）复制的报道，但它们在慢乙肝患者的转归及疗效的相关性仍缺乏明确的证据。本项目前期工作发现由11个miRNA组成的表达谱与慢乙肝干扰素治疗的应答密切关联，提示这些miRNA可能参与了拮抗HBV的复制周期。初步结果显示在这11个miRNA中，let-7f高表达能显著抑制HBV复制。本项目在此基础上，拟在体外和小鼠尾静脉注射模型中确认let-7f调控HBV复制的现象。在作用机制方面探索let-7f及家族成员是否通过靶向肝细胞核因子3（HNF3）水平调控HBV增强子的活性。另外通过基因芯片等方法寻找入选miRNA调控的靶基因，对候选靶基因是否参与调控HBV复制并确定其具体作用环节进行深入研究。本研究的结果有助于了解HBV感染慢性化过程中与宿主的相互拮抗的分

中文关键词： 小RNA；干扰素；乙肝病毒；；

英文摘要： microRNAs (miRNA) are a class of non-coding small RNA that plays an important role in the interaction between virus and the host. Although there have been several reports on the regulation of hepatitis B virus (HBV) replication by miRNAs, little evidence has been presented on the association between these miRNAs' expression levels and response and prognosis to antiviral therapy in chronic HBV patients. Our previous work demonstrated that an expression profile made up of 11 miRNAs are highly correlated with response to intereron therapy in chronic HBV patients, which suggests that these miRNAs are probably involved in the regulation of HBV life cycle. Preliminary experiments showed that among them, high level of let-7f was able to inhibit the replication of HBV. Based on these observations, we propose to further confirm the regulatory roles of let-7f in vivo using the HBV plasmid based tail vein injection model. Furthermore, we plan to test whether let-7f and its family members regulate HBV replication by modulating HNF3 (hepatocyte nuclear fator 3) level.In addition, we intend to perform microarrary analysis to find novel target genes of these miRNAs and examine the exact mechanism by which they regulate the HBV life cycle. The results of this project may help to deepen the understanding of the interplay bet

英文关键词： microRNA；Interferon；HBV；；