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大鼠糖尿病性心肌病的mRNA- miRNA综合分析

mRNA-miRNA integrative analysis of diabetes-induced cardiomyopathy in rats.

作者信息

Lopes Mariana B, Freitas Renata C, Hirata Mario H, Hirata Rosario, Rezende Adriana A, Silbiger Vivian N, Bortolin Raul H, Luchessi Andre D

机构信息

Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte. General Cordeiro de Farias Av., Natal, Rio Grande do Norte, 59012-570, Brazil.

Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo. 580 B17 Lineu Prestes Av., Butantan,05508-900. Sao Paulo, Brazil.

出版信息

Front Biosci (Schol Ed). 2017 Mar 1;9(2):194-229. doi: 10.2741/s483.

Abstract

An integrative analysis of miRNA and mRNA expression profiles in left ventricle (LV) of diabetes-induced rats was performed to elucidate the role of miRNAs and their mRNAs target in diabetic cardiomyopathy (DCM). mRNA (GSE4745) and miRNA (GSE44179) datasets were downloaded from Gene Expression Omnibus 2R (GEO2R) and differentially expressed mRNAs and miRNAs were selected. Cardiotoxicity-related mRNAs (n=7) were analyzed by Ingenuity Pathway Analyses 6 (IPA) and regulatory miRNAs (n=639) were identified using TargetScan 7.1. web dataset. The integrative analysis was performed between miRNAs differentially expressed in GSE44179 and regulatory TargetScan-detected miRNAs of mRNAs differentially expressed in GSE4745. and mRNAs were up-and-down regulated, respectively, in GSE4745 on days 3 and 42 after diabetes-induction. The regulatory miRNAs, rno-miR-877, rno-miR-320 and rno-miR-214 were down-regulated, and regulatory miRNAs, rno-miR-17, rno-miR-187, rno-miR-34a, rno-miR-322, rno-miR-188, rno-miR-532 and rno-miR-21, were up-regulated in GSE44179 dataset. These results are suggestive that and mRNAs and their regulatory miRNAs play a role in DCM pathogenesis and they may be potential circulating biomarkers to detect early cardiovascular complications in diabetic patients.

摘要

对糖尿病诱导大鼠左心室(LV)中的miRNA和mRNA表达谱进行综合分析,以阐明miRNA及其mRNA靶标在糖尿病性心肌病(DCM)中的作用。从基因表达综合数据库2R(GEO2R)下载mRNA(GSE4745)和miRNA(GSE44179)数据集,并选择差异表达的mRNA和miRNA。通过 Ingenuity Pathway Analyses 6(IPA)分析与心脏毒性相关的mRNA(n = 7),并使用TargetScan 7.1网络数据集鉴定调控性miRNA(n = 639)。对GSE44179中差异表达的miRNA与TargetScan检测到的GSE4745中差异表达的mRNA的调控性miRNA进行综合分析。在糖尿病诱导后的第3天和第42天,GSE4745中的mRNA分别上调和下调。在GSE44179数据集中,调控性miRNA rno-miR-877、rno-miR-320和rno-miR-214下调,而调控性miRNA rno-miR-17、rno-miR-187、rno-miR-34a、rno-miR-322、rno-miR-188、rno-miR-532和rno-miR-21上调。这些结果表明,[具体基因名称1]和[具体基因名称2]mRNA及其调控性miRNA在DCM发病机制中起作用,它们可能是检测糖尿病患者早期心血管并发症的潜在循环生物标志物。

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