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扩张型心肌病中枢纽基因和 microRNA 的综合分析。

Integrated Analysis of Hub Genes and miRNAs in Dilated Cardiomyopathy.

机构信息

Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, China.

出版信息

Biomed Res Int. 2020 Sep 15;2020:8925420. doi: 10.1155/2020/8925420. eCollection 2020.

DOI:10.1155/2020/8925420
PMID:33015184
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7512046/
Abstract

PURPOSE

The aim of this study is to identify hub genes and miRNAs by the miRNA-mRNA interaction network in dilated cardiomyopathy (DCM) disease.

METHODS

The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were selected using data of DCM patients downloaded from the GEO database (GSE112556 and GSE3585). Gene Ontology (GO) pathway analysis and transcription factor enrichment analysis were used for selecting DEMis, and the target mRNAs of DEMis were filtered by using miRDB, miRTarBase, and TargetScan. Cytoscape software was used to visualize the network between miRNAs and mRNAs and calculate the hub genes. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the mRNAs in the regulatory network.

RESULTS

A total of 9 DEMis and 281 DEMs were selected, from which we reconstructed the miRNA-mRNA network consisting of 7 miRNAs and 51 mRNAs. The top 10 nodes, miR-144-3p, miR-363-3p, miR-9-3p, miR-21-3p, miR-144-5p, miR-338-3p, ID4 (inhibitor of DNA binding/differentiation 4), miR-770-5p, PIK3R1 (p85 regulatory subunit of phosphoinositide 3-kinase (PI3K)), and FN1 (fibronectin 1), were identified as important regulators.

CONCLUSIONS

The study uncovered several important hub genes and miRNAs involved in the pathogenesis of DCM, among which, the miR-144-3p/FN1 and miR-9-3p/FN1 pathways may play an important role in myocardial fibrosis, which can help identify the etiology of DCM, and provide potential therapeutic targets.

摘要

目的

本研究旨在通过扩张型心肌病（DCM）疾病的 miRNA-mRNA 互作网络鉴定枢纽基因和 miRNA。

方法

从 GEO 数据库（GSE112556 和 GSE3585）下载 DCM 患者的数据，筛选差异表达的 miRNA（DEMis）和 mRNA（DEMs）。采用基因本体（GO）通路分析和转录因子富集分析筛选 DEMis，利用 miRDB、miRTarBase 和 TargetScan 筛选 DEMis 的靶基因。采用 Cytoscape 软件可视化 miRNA 和 mRNA 之间的网络，并计算枢纽基因。GO 和京都基因与基因组百科全书（KEGG）通路分析用于分析调控网络中的 mRNA。

结果

共筛选到 9 个 DEMis 和 281 个 DEMs，构建了由 7 个 miRNA 和 51 个 mRNA 组成的 miRNA-mRNA 网络。miR-144-3p、miR-363-3p、miR-9-3p、miR-21-3p、miR-144-5p、miR-338-3p、ID4（DNA 结合/分化抑制因子 4）、miR-770-5p、PIK3R1（磷酸肌醇 3-激酶（PI3K）p85 调节亚基）和 FN1（纤连蛋白 1）这 10 个节点被鉴定为重要的调节子。

结论

本研究揭示了一些参与 DCM 发病机制的重要枢纽基因和 miRNA，其中 miR-144-3p/FN1 和 miR-9-3p/FN1 通路可能在心肌纤维化中发挥重要作用，有助于确定 DCM 的病因，并为潜在的治疗靶点提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/03ca4aa04e34/BMRI2020-8925420.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/c68a4a64eed3/BMRI2020-8925420.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/9624587073bd/BMRI2020-8925420.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/03ca4aa04e34/BMRI2020-8925420.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/c68a4a64eed3/BMRI2020-8925420.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/9624587073bd/BMRI2020-8925420.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61d9/7512046/03ca4aa04e34/BMRI2020-8925420.003.jpg

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