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冠状动脉疾病的整合性微小RNA-信使核糖核酸分析

Integrated microRNA-mRNA analysis of coronary artery disease.

作者信息

Chen Fei, Zhao Xin, Peng Juan, Bo LinPing, Fan Bing, Ma Duan

机构信息

Department of Cardiology, Fifth Hospital of Fudan University, Shanghai, 200240, China.

出版信息

Mol Biol Rep. 2014 Aug;41(8):5505-11. doi: 10.1007/s11033-014-3426-9. Epub 2014 Jun 10.

Abstract

Although patients with coronary artery disease (CAD) have a high mortality rate, the pathogenesis of CAD is still poorly understood. The purpose of this study was to explore the underlying molecular mechanisms and potential target molecules for CAD. The platelet miRNA (GSE28858) and blood mRNA (GSE42148) expression profiles of patients with CAD and healthy controls were downloaded from Gene Expression Omnibus. Differentially expressed miRNAs and genes (DEGs) were identified by significant analysis of microarray algorithm after data preprocessing. Furthermore, the miRNA-target gene regulatory network was constructed based on miRecords database. The spearman correlation coefficients (ρ) between miRNAs and their target genes were calculated. Six up- (miR-340, miR-545, miR-451, miR454-5p, miR-624 and miR-585) and four down-regulated (miR-199a, miR-17-3p, miR-154 and miR-339) miRNAs were screened. Total 295 target genes of miR-545, miR-451, miR-585 and miR-154 were predicted. Among these 295 target genes, 7 genes were DEGs. Further analysis showed miR-545-TFEC and miR-585-SPOCK1 were highly positively correlated (ρ = 0.808091264; ρ = 0.874680776) in CAD samples. Therefore, differentially expressed miRNAs might participate in the pathogenesis of CAD by regulating their target genes.

摘要

尽管冠心病(CAD)患者死亡率很高,但其发病机制仍未完全明确。本研究旨在探索CAD潜在的分子机制和靶点分子。从基因表达综合数据库(Gene Expression Omnibus)下载CAD患者和健康对照者的血小板miRNA(GSE28858)和血液mRNA(GSE42148)表达谱。数据预处理后,通过微阵列算法的显著性分析鉴定差异表达的miRNA和基因(DEGs)。此外,基于miRecords数据库构建miRNA-靶基因调控网络。计算miRNA与其靶基因之间的斯皮尔曼相关系数(ρ)。筛选出6个上调(miR-340、miR-545、miR-451、miR454-5p、miR-624和miR-585)和4个下调(miR-199a、miR-17-3p、miR-154和miR-339)的miRNA。预测了miR-545、miR-451、miR-585和miR-154的总共295个靶基因。在这295个靶基因中,有7个是DEGs。进一步分析显示,在CAD样本中miR-545-TFEC和miR-585-SPOCK1高度正相关(ρ = 0.808091264;ρ = 0.874680776)。因此,差异表达的miRNA可能通过调控其靶基因参与CAD的发病机制。

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