Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation

Özet

Objective: We aimed to find crucial microRNAs (miRNAs) associated with the development of atrial fibrillation (AF), and then try to elucidate thepossible molecular mechanisms of miRNAs in AF.Methods: The miRNA microarray, GSE68475, which included 10 right atrial appendage samples from patients with persistent AF and 11 samplesfrom patients with normal sinus rhythm, was used for the analysis. After data preprocessing, differentially expressed miRNAs were screened using limma. Target genes of miRNAs were predicted using miRWalk2.0. We then conducted functional enrichment analyses for miRNA and targetgenes. Protein-protein interaction (PPI) network and module analyses for target genes were performed. Finally, transcription factors (TFs)-targetgenes regulatory network was predicted and constructed.Results: Seven genes, including CAMK2D, IGF2R, PPP2R2A, PAX6, POU3F2, YWHAE, and AP2A2, were targeted by TFs. Among these sevengenes, CAMK2D (targeted by miR-31-5p), IGF2R (targeted by miR-204-5p), PAX6 (targeted by miR-223-3p), POU3F2 (targeted by miR-204-5p),YWHAE (targeted by miR-31-5p), and AP2A2 (targeted by miR-204-5p) belonged to the top 10 degree genes in the PPI network. Notably, MiR204-5p, miR-31-5p, and miR-223-3p had more target genes. Besides, CAMK2D was enriched in some pathways, such as adrenergic signaling incardiomyocytes pathway and cAMP signaling pathway. YWHAE was enriched in the Hippo signaling pathway.Conclusion: miR-31-5p played a crucial role in cardiomyocytes by targeting CAMK2D and YWHAE via cAMP and Hippo signaling pathways. miR204 was involved in the progression of AF by regulating its target genes IGF2R, POU3F2, and AP2A2. On the other hand, miR-223-3p functionedin AF by targeting PAX6, which was associated with the regulation of apoptosis in AF. This study would provide a theoretical basis and potentialtherapeutic targets for the treatment of AF. (Anatol J Cardiol 2020; 23: 324-33)