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

Abstract

Xing Liu,1 Guoqiang Zhong,2 Wenbin Li,1 Yiqian Zeng,3 Mingxing Wu1 1Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, People’s Republic of China; 2Department of Cardiology, Guangxi Cardiovascular Institute, The First Affiliated Hospital of Guangxi Medical University, Guangxi, People’s Republic of China; 3Department of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, People’s Republic of ChinaCorrespondence: Yiqian ZengDepartment of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, Hunan, People’s Republic of ChinaEmail [email protected] WuDepartment of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, People’s Republic of China Email [email protected]: 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.Keywords: atrial fibrillation, competitive endogenous RNA, immune infiltration

Keywords

• atrial fibrillation
• competitive endogenous rna
• immune infiltration