通过荟萃分析鉴定与冠心病相关的关键 miRNA 和 mRNA。
Identification of key miRNAs and mRNAs related to coronary artery disease by meta-analysis.
机构信息
Department of Cardiovascular Medicine, The Third Hospital of Jilin University, No.126, Xiantai Street, Changchun, 130033, China.
Jilin Provincial Precision Medicine Key Laboratory for Cardiovascular Genetic Diagnosis, Changchun, 130033, China.
出版信息
BMC Cardiovasc Disord. 2021 Sep 16;21(1):443. doi: 10.1186/s12872-021-02211-2.
BACKGROUND
To illustrate the mechanism of miRNA and mRNA in coronary artery diseasen (CAD), differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed.
METHODS
The mRNA transcription profiles of GSE20680 (including 87 blood samples of CAD and 52 blood samples of control), GSE20681 (including 99 blood samples of CAD and 99 blood samples of control) and GSE12288 (including 110 blood samples of CAD and 112 blood samples of control) and the miRNA transcription profiles of GSE59421 (including 33 blood samples of CAD and 37 blood samples of control), GSE49823 (including 12 blood samples of CAD and 12 blood samples of control) and GSE28858 (including 13 blood samples of CAD and 13 blood samples of control) were downloaded from Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/ ). Then, the homogenous expressed mRNAs and miRNAs across the three mRNA transcription profiles and three miRNA transcription profiles were screened using the Fishers exact test in MetaDE. ES package. The weighted gene co-expression network analysis (WGCNA) was used to analyze gene modules. Additionally, the integrated miRNAs-targets regulatory network using the DEmiRNA and their targets was constructed using Cytoscape.
RESULTS
A total of 1201 homogenously statistically significant DEGs were identified including 879 up-regulated and 322 down-regulated DEGs, while a total of 47 homogenously statistically significant DEmiRNAs including 37 up-regulated and 10 down-regulated DEmiRNAs in CAD compared with the controls across the three mRNA transcription profiles and the three miRNA transcription profiles. A total of 5067 genes were clustered into 9 modules in the training dataset, among which, 8 modules were validated. In the miRNAs-targets network, there existed 267 interaction relationships among 5 miRNAs (hsa-miR-361-5p, hsa-miR-139-5p, hsa-miR-146b-5p, hsa-miR-502-5p and hsa-miR-501-5p) and 213 targets. CAV1 could be the target of hsa-miR-361-5 while HSF2 was the target of both hsa-miR-361-5p and hsa-miR-146b-5p. CAV1 was significantly enriched in the GO term of regulation of cell proliferation.
CONCLUSION
hsa-miR-361-5p, has-miR-146b-5p, CAV1 and HSF2 could play an important role in CAD.
背景
为了阐明 miRNA 和 mRNA 在冠状动脉疾病（CAD）中的作用机制，分析了差异表达的 microRNAs（DEmiRNAs）和基因（DEGs）。
方法
从基因表达综合数据库（GEO；http://www.ncbi.nlm.nih.gov/geo/ ）下载 GSE20680（包括 87 例 CAD 患者和 52 例对照者的血液样本）、GSE20681（包括 99 例 CAD 患者和 99 例对照者的血液样本）和 GSE12288（包括 110 例 CAD 患者和 112 例对照者的血液样本）的 mRNA 转录谱，以及 GSE59421（包括 33 例 CAD 患者和 37 例对照者的血液样本）、GSE49823（包括 12 例 CAD 患者和 12 例对照者的血液样本）和 GSE28858（包括 13 例 CAD 患者和 13 例对照者的血液样本）的 miRNA 转录谱。然后，使用 MetaDE 中的 Fisher 精确检验筛选出这三个 mRNA 转录谱和三个 miRNA 转录谱中具有同质性表达的 mRNAs 和 miRNAs。采用加权基因共表达网络分析（WGCNA）分析基因模块。此外，使用 Cytoscape 构建包含差异表达 miRNA 及其靶标的整合 miRNA-靶标调控网络。
结果
在三个 mRNA 转录谱和三个 miRNA 转录谱中，CAD 与对照组相比，共鉴定出 1201 个具有统计学意义的均匀差异表达基因，包括 879 个上调和 322 个下调的 DEGs，以及 47 个具有统计学意义的均匀差异表达 miRNA，包括 37 个上调和 10 个下调的 DEmiRNA。在训练数据集，5067 个基因聚类为 9 个模块，其中 8 个模块得到验证。在 miRNA-靶标网络中，存在 5 个 miRNA（hsa-miR-361-5p、hsa-miR-139-5p、hsa-miR-146b-5p、hsa-miR-502-5p 和 hsa-miR-501-5p）和 213 个靶标之间存在 267 个相互作用关系。CAV1 可能是 hsa-miR-361-5 的靶标，而 HSF2 是 hsa-miR-361-5p 和 hsa-miR-146b-5p 的共同靶标。CAV1 显著富集于细胞增殖调控的 GO 术语中。
结论
hsa-miR-361-5p、hsa-miR-146b-5p、CAV1 和 HSF2 可能在 CAD 中发挥重要作用。
Zotero 插件