LncRNA-miRNA相互对话调控脑缺血后血管新生及其机制研究

项目名称： LncRNA-miRNA相互对话调控脑缺血后血管新生及其机制研究

项目编号： No.81471243

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邓志锋

作者单位： 上海交通大学

项目金额： 70万元

中文摘要： 缺血性脑卒中治疗的关键是尽快恢复缺血区的血供，全面阐明脑卒中后血管新生的调控机制是制定有效治疗性血管新生策略的首要前提。lncRNAs的最新研究发现，MEG3与血管新生信号通路密切相关，lncRNAs可通过MRE结合位点与miRNAs之间相互调控。我们在前期研究中对脑卒中大鼠脑组织进行了测序和生物信息学分析，发现脑缺血后MEG3、Let-7及其靶基因表达出现显著变化，而且都存在相同MRE结合位点。结合ceRNA调控假说，我们推断以MEG3、Let-7为代表的lncRNAs- miRNAs相互对话参与了脑卒中后血管新生的调控。本项目拟在前期研究基础上，通过系列实验深入探讨MEG3、Let-7及其靶基因在血管新生过程中的变化规律及其相互间调控关系，明确lncRNAs- miRNAs相互对话网络对血管新生的调控功能和作用途径，以期进一步阐明脑卒中后血管新生的分子调控机制。

中文关键词： 血管新生；长链非编码RNA；微小RNA；脑缺血

英文摘要： The recovery of blood supply as soon as possible is the key point for treating ischemic stroke. Elucidation the regulation mechanisms thoroughly on post-ischemia angiogenesis is the central premise for developing effective therapeutic strategy of angiogenesis. Recent lncRNAs-related studies indicated that MEG3 is closely related to angiogenesis signaling pathway. LncRNAs can interact with miRNAs via binding microRNA response elements (MREs). In our preliminary study，through analyzing brain tissue after stroke by deep sequencing combine bioinformatics analysis, we found the expression level of lncRNA MEG3, microRNA-Let-7 and its target gene changed remarkably, and these molecules shared a common MRE bingding site. Combination the competing endogenous RNAs (ceRNAs) regulation hypothesis, we assumed that a novel lncRNAs-miRNAs crosstalk mechanisms such as MEG3 and Let-7 may be involved in regulating angiogenesis after brain stroke. Based on our previous research results, we want to define the regulatory role and signaling pathway of lncRNAs-miRNAs crosstalk network in angiogenesis and clarify the molecular regulation mechanisms on angiogenesis after stroke by exploring the change rules and their interreactive relationships among lncRNA MEG3, Let-7 and its target in the process of angiogenesis.

英文关键词： angiogenesis;LncRNA;miRNA;cerebral ischemia