Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

Manman Wang; Guoying An; Benxuan Wang; Yuanyuan Chen; Genli Liu; Xin Wang; Shuai Liu; Daozou Zhang; Dandan Sun; Yanyan Zhang; Tong Shen; Xiangting Li

doi:10.3389/fcvm.2023.1099124

Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

Front Cardiovasc Med. 2023 Apr 27:10:1099124. doi: 10.3389/fcvm.2023.1099124. eCollection 2023.

Authors

Manman Wang^#¹, Guoying An^#², Benxuan Wang^#³, Yuanyuan Chen¹, Genli Liu¹, Xin Wang¹, Shuai Liu¹, Daozou Zhang¹, Dandan Sun¹, Yanyan Zhang⁴, Tong Shen¹, Xiangting Li¹

Affiliations

¹ Jining Key Laboratory for Diagnosis and Treatment of Cardiovascular Diseases, Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, China.
² Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Department of Cardiac Surgery, Affiliated Hospital of Jining Medical University, Jining, China.
³ Department of Neurology, Jinnan Hospital, Tianjin, China.
⁴ Admission and Patient Service Center, Affiliated Hospital of Jining Medical University, Jining, China.

^# Contributed equally.

Abstract

Objective: Long non-coding RNAs (lncRNAs) play pivotal roles in the transcriptional regulation of atrial fibrillation (AF) by acting as competing endogenous RNAs (ceRNAs). In the present study, the expression levels of lncRNAs of sinus rhythm (SR) patients and AF patients were investigated with transcriptomics technology, and the lncRNA-miRNA-mRNA network based on the ceRNA theory in AF was elaborated.

Methods: Left atrial appendage (LAA) tissues were obtained from patients with valvular heart disease during cardiac surgery, and they were divided into SR and AF groups. The expression characterizations of differentially expressed (DE) lncRNAs in the two groups were revealed by high-throughput sequencing methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the lncRNA-miRNA-mRNA-mediated ceRNA network was constructed.

Results: A total of differentially expressed 82 lncRNAs, 18 miRNAs, and 495 mRNAs in human atrial appendage tissues were targeted. Compared to SR patients, the following changes were found in AF patients: 32 upregulated and 50 downregulated lncRNAs; 7 upregulated and 11 downregulated miRNAs; and 408 upregulated and 87 downregulated mRNAs. A lncRNA-miRNA-mRNA network was constructed, which included 44 lncRNAs, 18 miRNAs, and 347 mRNAs. qRT-PCR was performed to verify these findings. GO and KEGG analyses suggested that inflammatory response, chemokine signaling pathway, and other biological processes play important roles in the pathogenesis of AF. Network analysis based on the ceRNA theory identified that lncRNA XR_001750763.2 and Toll-like receptor 2 (TLR2) compete for binding to miR-302b-3p. In AF patients, lncRNA XR_001750763.2 and TLR2 were upregulated, and miR-302b-3p was downregulated.

Conclusion: We identified a lncRNA XR_001750763.2/miR-302b-3p/TLR2 network based on the ceRNA theory in AF. The present study shed light on the physiological functions of lncRNAs and provided information for exploring potential treatments for AF.

Keywords: atrial fibrillation; bioinformatics analysis; competing endogenous RNA; long non-coding RNAs; microRNAs.

Grants and funding

This work was funded by the PhD Research Foundation of Affiliated Hospital of Jining Medical University (Grant Number: 2021-BS-005), the Key Research and Development Program of Jining (Grant Number: 2021YXNS104), the Jining Medical University Research Fund for Academician Lin He New Medicine (Grant Number: JYHL2018FZD08), and the Nursery Research Project of Affiliated Hospital of Jining Medical University (Grant Number: MP-ZD-2022-001).