Lnc-TRMT2A竞争性结合miR-520a调控炎性通路在精神分裂症发病中的作用研究

项目名称： Lnc-TRMT2A竞争性结合miR-520a调控炎性通路在精神分裂症发病中的作用研究

项目编号： No.81501827

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 周易

作者单位： 四川大学

项目金额： 18万元

中文摘要： 研究发现炎性反应在精神分裂症（SZ）发病机理中起重要作用，而非编码RNA通过参与炎性通路的调控，与SZ发生发展密切相关。课题组前期发现lnc-TRMT2A上rs3757位点与SZ易感性相关；lnc-TRMT2A在SZ患者中表达上调；并发现其存在miR-520a的结合靶点。我们推测：lnc-TRMT2A在SZ患者中表达升高，会竞争性增加与miR-520a的结合，导致后者表达下降，从而减弱miR-520a对RELA的负调节，增加RELA的转录，进而升高血清中炎症因子水平，通过炎症途径参与SZ的发病机制。本研究拟揭示lnc-TRMT2A和miR-520a表达与SZ发病的关系；并从细胞水平探索lnc-TRMT2A结合miR-520a调控下游炎症通路在SZ发病中的作用机制。本研究首次结合LncRNA、miRNA及炎性通路探讨SZ的发病机制，有助于进一步阐明lncRNA在SZ中的作用及筛查新的标志物。

中文关键词： 精神分裂症；长链非编码RNA；微小RNA

英文摘要： Schizophrenia(SZ) is being thought of as systemic illness in which inflammation is involved. Non-coding RNAs (lncRNA and miRNA) were reported to participate in the onset of schizophrenia though post-transcriptional regulation in inflammation. Our pervious finding that rs3757, a SNP located in lnc-TRMT2A—associated with SZ patients, and lnc-TRMT2A was up-regulated in SZ patients. Futhermore, we predicted that miR-520a binding site existed in lnc-TRMT2A. Combining our previous work with literature reports, we speculate that: lnc-TRMT2A, combining miR-520a as a competing endogenous RNA, was up-regulated in SZ, which leads to the down-regulation miR-520a, and in turn, leads to the up- regulation of RELA gene—consequently involved in inflammation and SZ pathogenesis. This research aims to reveal the relationship of miR-520a and lnc-TRMT2A expression with SZ pathogenesis and to explore the mechanism of lnc-TRMT2A functions in SZ through inflammation in cellular level. As the first time to combine LncRNA, miRNA and inflammatory pathways in SZ, this study is significant in illuminating the roles of non-conding RNA in SZ pathogenesis, and will provide new potential in screening biomarkers for SZ diagnosis and treatment.

英文关键词： schizophrenia;long noncoding RNA;microRNA