Bioinformatics Analysis of Competing Endogenous RNA Network and Immune Infiltration in Atrial Fibrillation

Abstract

Background. There is still no clear understanding of the pathogenesis of atrial fibrillation (AF). For this purpose, we used integrated analysis to uncover immune infiltration characteristics and investigated their relationship with competing endogenous RNA (ceRNA) network in AF. Methods. Three AF mRNA data sets (GSE14975, GSE79768, and GSE41177) were integrated using the SVA method from Gene Expression Omnibus (GEO). Together with AF circRNA data set (GSE129409) and miRNA data set (GSE70887) from GEO database, we built a ceRNA network. Then hub genes were screened by the Cytoscape plug-in cytoHubba from a protein-protein interaction (PPI) network. As well, CIBERSORT was employed to investigate immune infiltration, followed by Pearson correlation coefficients to unravel the correlation between AF-related infiltrating immune cells and hub genes. Ulteriorly, circRNA-miRNA-mRNA regulatory axises that could be immunologically related to AF were obtained. Results. Ten hub genes were identified from the constructing PPI network. The immune infiltration analysis revealed that the number of monocytes and neutrophils was higher, as well as the number of dendritic cells activated and T cells regulatory (Tregs) was lower in AF. Seven hub genes (C5AR1, CXCR4, HCK, LAPTM5, MPEG1, TLR8, and TNFSF13B) were associated with those 4 immune cells ( P < 0.05 ). We found that the circ_0005299–miR-1246–C5AR1 and circRNA_0079284-miR-623-HCK/CXCR4 regulatory axises may be associated with the immune mechanism of AF. Conclusion. The findings of our study provide insights into immuno-related ceRNA networks as potential molecular regulators of AF progression.

Analyses of m6A regulatory genes and subtype classification in atrial fibrillation

“…A recent review also proposed the concept of immune remodeling in AF, highlighting significant changes in the immune system during AF and its interactions with the cellular and environmental factors involved in AF initiation and maintenance ( Yao et al, 2022 ). Studies suggest that dendritic cells and regulatory T cells may be related to AF pathogenesis ( Li et al, 2021 ; Xiao et al, 2021 ; Liu et al, 2022 ; Xie et al, 2022 ). The PD-1/PD-L1 pathway plays a key role in AF immunomodulation by regulating T-cell activation and promoting inflammatory factor secretion ( Liu et al, 2015 ; Chang et al, 2022 ).…”