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Bioinformatics analysis of the circRNA-miRNA-mRNA network for atrial fibrillation.

Xing Liu | Yiqian Zeng | Zhao Liu | Wenbin Li | Lei Wang | Mingxing Wu
Medicine | 2022

Atrial fibrillation (AF) is a chronic and progressive disease, with advancing age, the morbidity of which will increase exponentially. Circular ribonucleic acids (RNAs; circRNAs) have gained a growing attention in the development of AF in recent years. The purpose of this study is to explore the mechanism of circRNA regulation in AF, in particular, the intricate interactions among circRNA, microRNA (miRNA), and messenger RNA (mRNA). Three datasets (GSE129409, GSE68475, and GSE79768) were obtained from the Gene Expression Omnibus database to screen differentially expressed (DE) circRNAs, DE miRNAs, and DE mRNAs in AF, respectively. Based on circRNA-miRNA pairs and miRNA-mRNA pairs, a competing endogenous RNAs (ceRNAs) network was built. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of DE mRNAs in the network were performed and protein-protein interaction (PPI) networks were established to identify hub genes. Finally, a circRNA-miRNA-hub gene subnetwork was constructed. A total of 103 DE circRNAs, 16 DE miRNAs, and 110 DE mRNAs were screened in AF. Next, ceRNAs network in AF was constructed with 3 upregulated circRNAs, 2 downregulated circRNAs, 2 upregulated miRNAs, 2 downregulated miRNAs, 17 upregulated mRNAs, and 24 downregulated mRNAs. Thirty GO terms and 6 KEGG pathways were obtained. Besides, 6 hub genes (C-X-C chemokine receptor type 4 [CXCR4], C-X-C chemokine receptor type 2 [CXCR2], C-X-C motif chemokine 11 [CXCL11], neuromedin-U, B1 bradykinin receptor, and complement C3) were screened from constructing a PPI network. Finally, a circRNA-miRNA-hub gene subnetwork with 10 regulatory axes was constructed to describe the interactions among the differential circRNAs, miRNA, and hub genes. We speculated that hsa_circRNA_0056281/hsa_circRNA_0006665 -hsa-miR-613-CXCR4/CXCR2/CXCL11 regulatory axes and hsa_circRNA_0003638-hsa-miR-1207-3p-CXCR4 regulatory axis may be associated with the pathogenesis of AF.

Pubmed ID: 36042613

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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Cytoscape (tool)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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