The Construction and Comprehensive Analysis of a ceRNA Immunoregulatory Network and Tissue-Infiltrating Immune Cells in Atrial Fibrillation

Abstract

Background: At present, the mechanisms behind atrial fibrillation (AF) pathogenesis are still unclear. We construct a ceRNA immunoregulatory network to further understand the mechanism of AF. Methods: Four AF mRNA datasets from the Gene Expression Omnibus (GEO) database were integrated by SVA method. AF-related immune genes (AF-IRGs) were selected via combining ImmPort database with the genes in the module most associated with AF obtained by a weighted gene coexpression network analysis (WGCNA). Then, circRNA and miRNA expressions from the GEO database were extracted and mapped with related databases. Next, an immune-related circRNA-miRNA-mRNA ceRNA network was constructed and hub genes were filtered from a protein-protein interaction (PPI) network, and the differentially expressed (DE) hub genes in AF were further screened. Additionally, immune infiltration was investigated in AF by using CIBERSORT. Subsequently, the relationships between DE hub genes and AF-related infiltrating immune cells were performed by using Pearson correlation coefficients. Ulteriorly, the immune-cells-related ceRNA subnetwork in AF was built. Results: A total of 95 AF-IRGs were detected, and an immune-related ceRNA network in AF was constructed with 12 circRNAs, 7 miRNAs and 50 mRNAs. The immune infiltration analysis indicated that a higher level of neutrophils, as well as a lower level of T cells regulatory (Tregs) and NK cells activated in AF. Four DE hub genes (CXCL12, IL7R, TNFSF13B, CD8A) were associated with Tregs or NK cells activated immune cells (P < 0.05). Tregs or NK cells activated immune cells-related ceRNA subnetwork including 5 circRNAs (has_circ_0001190, has_circ_0006725, has_circ_0079284, has_circ_0005299, and has_circ_0002103), 4 miRNAs (has-miR-198, has-miR-623, has-miR-1246, and has-miR -339-3p) and 4 DE hub genes was eventually constructed in AF. Conclusion: Our results provide new insights into the molecular mechanisms governing AF progression from the perspective of immune-related ceRNA network.

Identification and validation of oxidative stress-related genes in patients with atrial fibrillation

“…However, the speci c underlying mechanisms of these genes in AF require further clari cation. [24,25]. Our study indicates that hsa-miR-129-5p, hsa-miR-495-3p, hsa-miR-200c-3p, hsa-miR-92b-3p, and hsa-miR-429 are involved in the pathophysiological processes of atrial brillation (AF), suggesting their potential as targets for the prevention and treatment of AF.…”

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

“…And they validated IL-6-miR-210 inhibits Tregs function by targeting Foxp3 to promote atrial fibrosis. Recently, we downloaded immune genes from the database and constructed the immune cell-related ceRNA subnetwork through bioinformatics analysis, which the results showed that Tregs were also underexpressed in atrial auricular tissue of AF [ 37 ]. One more study revealed that Tregs alleviate myocardial fibrosis and cardiac hypertrophy in hypertensive mice caused by angiotensin II [ 38 ].…”

Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System

“…Yang et al (2022) pointed out four other hub genes, including CXCL12, LTBP1, LOXL1, and IGFBP3 [ 56 ]. The cytokine CXCL12, which recruits monocytes and lymphocytes, was also indicated by Liu et al (2021) as a hub DEG in AF along with IL7R, TNFSF13B, and CD8A associated with regulatory T cells or natural killer-cell-activated immune cells [ 57 ]. These data show that CXCL12 plays a vital role in regulating the local inflammatory response and immune cell infiltration.…”