药源性长QT综合征：hERG抑制剂诱导的转录后调控网络

项目名称： 药源性长QT综合征：hERG抑制剂诱导的转录后调控网络

项目编号： No.31301094

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 徐建凯

作者单位： 哈尔滨医科大学

项目金额： 22万元

中文摘要： hERG钾通道抑制剂是药源性长QT综合征(LQTS)的主要诱因,探讨LQTS发生机制并开发有效生物学标记,从而防治心源性猝死的发生具有重要意义。本项目从全基因组的角度，探索hERG抑制剂诱导的miNRA转录后调控机制，解释药源性LQTS的发生机理，提供潜在的早期诊断LQTS生物学标记。项目整合 mRNA和miRNA表达谱、miRNA-靶基因关系、转录因子-miRNA关系、生物学通路等数据资源，应用生物信息学方法筛选转录后调控系统中药源性LQTS特异激活的miRNA以及其调控的通路，对这些风险miRNA进行优先级评估，并将结果进行生物学证实。该项研究预期结果将进一步阐明药源性LQTS发生的分子机制，助推LQTS生物标记的研发，为筛查高风险药源性LQTS病患提供源头创新性工作。

中文关键词： hERG；微小RNA；转录因子；模块；风险网络

英文摘要： The hERG potassium channel inhibitor is the main cause of drug-induced long QT syndrome (LQTS), and it is a significant issue to investigate its mechanism and to develop effective biomarkers for avoiding sudden cardiac death induced by LQTS.This project from the perspective of the whole genome for the first time, explores the miRNA mediated post-transcriptional regulatory mechanism which is induced by hERG inhibitor，to explain the mechanism of drug-induced LQTS，and will provide potential biomarkers of drug-induced LQTS. The project will combine mRNA and miRNA expression profiling, miRNA-target gene relationship, the transcription factor-miRNA relationship, biological pathways and other data resources, and apply bioinformatics method to high-throughput screen specific activated miRNAs and their regulatory pathways in the post-transcriptional regulatory system induced by hERG inhibitor, and assess the riskiness of these drug-induced LQTS related miRNAs, part results of which will be further validated by biological experiments. The study is to elucidate the molecular mechanisms of the drug-induced LQTS, and to provide the source of innovative work for the development of effective biomarkers in screening the patients with high-risk drug-induced LQTS.

英文关键词： hERG；microRNA；Transcription factor；Module；Risk network