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

Abstract

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.

Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure

“…Notably, upregulation of cXcR4 expression was observed in patients with atrial fibrillation (AF) a decade ago (48). Recently, a flurry of bioinformatics analyses of clinical high-throughput data sets revealed that cXcR4 is a potent hub gene strongly associated with the pathogenesis of AF (49)(50)(51)(52). Previous studies with a mouse model of AF suggested that cXcR4 antagonist AMd3100 can treat AF by ameliorating calcium mishandling and tissue inflammation (50,52).…”

Identification of potentially functional circRNAs and prediction of the circRNA-miRNA-hub gene network in mice with primary blast lung injury

“…The advanced options were set as degree cutoff = 2, haircut, node score cutoff = 0.2, k-core = 2, and max depth = 100 [ 24 ]. In addition, hub genes in the PPI network were filtered by the Maximal Clique Centrality (MCC) arithmetic of the Cytoscape plug-in cytoHubba, which ranks nodes according to their attributes in the network, mining key genes (hub genes) and sub networks [ 25 , 26 ], the top ten nodes ranked by the MCC algorithm were considered as hub genes.…”

Bioinformatics analysis of the potentially functional circRNA-miRNA-mRNA network in breast cancer

“…Using bioinformatics data to simplify the circRNA-miRNA-mRNA interactions, which are comprised of such complicated processes, can shed light on in vitro and in vivo investigations. For example, in the bioinformatics study of Liu et al [ 5 ], it was emphasized that hsa_circRNA_0003638 may play a role in the pathogenesis of atrial fibrillation by targeting the CXCR4 gene via hsa-miR-1207-3p. Similarly, Hu et al [ 6 ] suggested that the interaction of hsa_circ_0009581 / hsa-miR-150-5p , and hsa_circ_0001947 / hsa-miR-454-3p may play a role in the AML cancer process.…”