microRNA调控心衰关键致病基因网络分析研究.doc

  microRNA 调控心衰关键致病基因网络分析 研究# 朱文良，杜智敏** 5 10 15 20 25 30 35 40 45 （哈尔滨医科大学附属二院临床药理研究所，哈尔滨 150001） 摘要：目的 通过网络分析研究 microRNAs（miRNAs）对心衰关键致病基因的调控作用， 为心衰的防治提供理论依据。方法 采用 Cytoscape 软件建立心肌缺血致病基因与心衰致病 基因相互作用网络，计算相互作用的超几何概率以寻找到心衰关键致病基因，并联合检索 miRSel 和 miRecords miRNA 靶基因数据库，构建 miRNA-心衰关键致病基因调控关系，从 中筛选出富集调控心肌纤维化或心肌功能的 miRNA 心衰防治新靶点。结果 通过计算超几 何概率，共寻找到 25 个心衰关键致病基因，而 miRNA-基因调控关系分析揭示出有 6 个 miRNAs 显著富集调控这些基因的表达，它们分别是 let-7a、miR-1、miR-16、miR-20a、miR-21、 miR-29b。结论 miRNAs 可通过富集调控心衰关键致病基因在心衰病理发展过程中起到重要 作用，提示上述 miRNAs 很可能成为心衰防治的新靶点。 关键词：心衰；心肌缺血；网络分析；microRNA 中图分类号：R96 Network Analysis of Key Pathogenic Gene-MicroRNA Regulatory Relationship in Heart Failure Zhu Wenliang, Du zhimin (Institute of Clinical Pharmacology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001) Abstract: Aim By applying network analysis on key disease-causing genes and microRNA (miRNA) regulatory relationships in heart failure, a reasonable drug target for heart failure prevention and treatment strategy that is based on miRNA is found and the theoretical basis is provided. Methods Cytoscape was used to establish human protein-protein interaction network, for myocardial ischemic disease and heart failure related genes. The hypergeometric probability of protein interaction was calulated to search for key pathogenic gene in heart failure. Joint retrieval of the miRSel and the miRecords miRNA target gene databases enabled building the miRNA-key pathogenic gene regulatory relationship in enriched regulation of myocardial fibrosis or myocardial functional changes. In the end, the reasonable miRNA-based drug targets for heart failure prevention and treatment could be revealed. Results By calculating the hypergeometric probability values, we found a total of 25 of key pathogenic genes of heart failure. Our netwrok analysis also revealed the regulatory relationship between miRNA-these genes. Six miRNAs that were significantly enriched in the regulation of expression of these genes are let-7a