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MicroRNA Regulatory Network Revealing the Mechanism of Inflammation in Atrial Fibrillation.

ABSTRACT: Atrial fibrillation (AF) is a highly prevalent condition associated with high morbidity and mortality that can cause or exacerbate heart failure and is an important risk factor for stroke. AF is the disorganized propagation of electrical activity in the atrium, which prevents organized contractions. However, the effect of microRNAs and the patterns of the regulatory network of AF remain vague.The mRNA expression data of atrial tissue splices from 3 conditions - permanent atrial fibrillation (AF), sinus rhythm (SR), and human left ventricular non-failing myocardium (LV) - were downloaded from GSE2240 and the differentially expressed genes (DEGs) between the 3 kinds of samples were calculated. Then we constructed 3 miRNA-DEGs networks and these networks were integrated to construct the final merged AF-related microRNA regulatory network. Finally, we constructed the miRNA-inflammation networks to detect the roles of miRNAs in inflammation development of AF.This network included 108 DEGs, and 27 microRNAs and DEGs are regulated by both microRNAs. We found that a sub-network composed by miR-124, miR-183, miR-215, miR-192, and a DEG of EGR1 were all represents in these 3 networks. Based on functional enrichment analysis, some biological process, such as energy and glucan metabolic process and heart and blood vessel development, were found to be regulated by miRNAs in AF. Some miRNAs, such as miR-26b and miR-355p, were involved in inflammation in AF.In conclusion, the microRNA regulatory network sheds new light on the molecular mechanism of AF with this non-coding regulated model.

SUBMITTER: Zhang H

PROVIDER: S-EPMC4651320 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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MicroRNA Regulatory Network Revealing the Mechanism of Inflammation in Atrial Fibrillation.

Zhang Hao H Liu Liming L Hu Jianguo J Song Long L

Medical science monitor : international medical journal of experimental and clinical research 20151114

<h4>Background</h4>Atrial fibrillation (AF) is a highly prevalent condition associated with high morbidity and mortality that can cause or exacerbate heart failure and is an important risk factor for stroke. AF is the disorganized propagation of electrical activity in the atrium, which prevents organized contractions. However, the effect of microRNAs and the patterns of the regulatory network of AF remain vague.<h4>Material and methods</h4>The mRNA expression data of atrial tissue splices from 3 ...[more]

PMID: 26567235

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Project description:Background Circular RNA (circRNA) is a noncoding RNA that forms a closed-loop structure, and its abnormal expression may cause disease. We aimed to find potential network for circRNA-related competitive endogenous RNA (ceRNA) in atrial fibrillation (AF). Methods The circRNA, miRNA, and mRNA expression profiles in the heart tissue from AF patients were retrieved from the Gene Expression Omnibus database and analyzed comprehensively. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified, followed by the establishment of DEcircRNA-DEmiRNA-DEmRNA regulatory network. Functional annotation analysis of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. In vitro experiment and electronic validation were used to validate the expression of DEcircRNAs, DEmiRNAs, and DEmRNAs. Results A total of 1611 DEcircRNAs, 51 DEmiRNAs, and 1250 DEmRNAs were identified in AF. The DEcircRNA-DEmiRNA-DEmRNA network contained 62 circRNAs, 14 miRNAs, and 728 mRNAs. Among which, two ceRNA regulatory pairs of hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 were identified. In addition, six miRNA-mRNA regulatory pairs including hsa-miR-34c-5p-INMT, hsa-miR-1253-DDIT4L, hsa-miR-508-5p-SMOC2, hsa-miR-943-ACTA1, hsa-miR-338-3p-WIPI1, and hsa-miR-199a-3p-RAP1GAP2 were also obtained. MTOR was a significantly enriched signaling pathway of host gene of DEcircRNAs. In addition, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy were remarkably enriched signaling pathways of DEmRNAs in DEcircRNA-DEmiRNA-DEmRNA regulatory network. The expression validation of hsa-circRNA-402565, hsa-miR-34c-5p, hsa-miR-188-5p, SPON1, DDIT4L, SMOC2, and WIPI1 was consistent with the integrated analysis. Conclusion We speculated that hsa-circRNA-100053-hsa-miR-455-5p-TRPV1 and hsa-circRNA-005843-hsa-miR-188-5p-SPON1 interaction pairs may be involved in AF.

Dataset Information

MicroRNA Regulatory Network Revealing the Mechanism of Inflammation in Atrial Fibrillation.

Publications

MicroRNA Regulatory Network Revealing the Mechanism of Inflammation in Atrial Fibrillation.

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