HuD及其靶标lncRNA对阿尔茨海默病关键相关基因的调控机制

项目名称： HuD及其靶标lncRNA对阿尔茨海默病关键相关基因的调控机制

项目编号： No.81671056

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 李华玲

作者单位： 扬州大学

项目金额： 25万元

中文摘要： 相关基因表达或功能失调与阿尔茨海默病(AD)的发生发展密切相关，但这些基因的调控机制远未得到阐明。申请者前期研究发现：1) RNA结合蛋白HuD水平在AD病人脑的颞上回区显著上调；2) HuD转基因小鼠的皮层和海马区APP，BACE1以及lncRNA BACE1AS表达升高并伴有明显的Aβ沉积；3) HuD结合包括BACE1AS在内的57个lncRNA；4）HuD稳定BACE1AS RNA。基于上述结果，我们假设：HuD可能通过与AD相关lncRNA互作影响关键AD相关基因的表达，进而影响AD过程中Aβ的沉积。本课题将在前期工作的基础上，进一步探讨HuD及其相关lncRNA对关键AD相关基因的表达的影响，探讨HuD对与之结合的lncRNA 水平及功能的影响，探讨HuD是否介导lncRNA对关键AD相关基因的表达的调控。这些研究不仅有助于解析AD的发病机制，也将为AD的临床治疗提供实验依据

中文关键词： 阿尔茨海默病；RNA；结合蛋白；HuD；淀粉样蛋白β；长链非编码RNA；转录后调控

英文摘要： The expression or dysfunction of related gene is closely associated with the occurrence and development of Alzheimer's disease (AD). However, the regulatory mechanism of these genes is far from being clarified. Our preliminary study showed: 1) the expression of HuD(RNA binding protein) in superior temporal gyrus (STG) from patients with AD was significantly increased. 2) the expression of APP,BACE1,and BACE1AS (lncRNA) was also elevated accompanied by obviously Aβ deposition in the cortex and hippocampus of HuD transgenic mouse. 3) HuD combined with 57 lncRNA including BACE1AS. 4) HuD stabilized the BACE1AS RNA. Based on the above results, we hypothesize that HuD may affect the expression of key AD-related genes by interacting with AD-related lncRNA, then affect the deposition of Aβ. This project will further investigate the regulatory effect of HuD and AD-related lncRNA on the expression of key AD-related gene, discuss the interaction between HuD and AD-related lncRNA, explore whether HuD mediates the regulation of lncRNA on key AD-related gene. This study will not only help to resolve the pathogenesis of AD, but also provide experimental evidence for clinical treatment of AD.

英文关键词： Alzheimer disease;RNA binding protein HuD;β-amyloid protein;long non-coding RNA ;posttranscriptional regulation