Identification of Circular RNA-MicroRNA-Messenger RNA Regulatory Network in Atrial Fibrillation by Integrated Analysis

Abstract

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.

Hsa_circ_0091581 promotes glioma progression by regulating RMI1 via sponging miR-1243-5p

“…To determine the mechanism of action of hsa_circ_0091581 on glioma proliferation, migration, and invasion, we used the results described in the literature that suggested that circRNAs can play a regulatory role by adsorbing miRNAs [30][31][32]. Hsa_circ_0001785 sponges miR-942 to regulate breast cancer progression [33]; hsa_circ_0005556 sponges miR-4270 to facilitate gastric cancer progression [34]; and hsa_circ_0004913 act as a sponge for miR-184 and is thus involved in the progress of hepatocellular carcinoma [35].…”

Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases

“…MFN2 is the host gene of hsa_circRNA_100053. MFN2 could regulate heart failure-related mitophagy by altering the mitochondrial membrane potential, suggesting the role of circRNA_100053 in mitophagy [ 123 ]. In addition, the circRNA ACR attenuated myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/FAM65B pathway [ 124 ].…”

Exosomes and Exosomal Non-coding RNAs Are Novel Promises for the Mechanism-Based Diagnosis and Treatments of Atrial Fibrillation

“…Another RNA-seq analysis in the patients with the PAF and PsAF found an increase of circRNAs from PAF transition to PsAF, accompanied by miRNAs down-regulation ( 168 ). According to an analysis of DE-circRNAs and ceRNAs network in the AF patients from the GEO database, 376 DE-circRNAs were identified, which were enriched in the cytokine-cytokine receptor interaction, and two ceRNAs pairs were identified (circRNA-100053- miR-455-5p-TRPV1 and circRNA-005843- miR-188-5p-SPON1) ( 169 , 170 ).…”