Integrative identification of hub genes in development of atrial fibrillation related stroke

Kai Huang; Xi Fan; Yuwen Jiang; Sheng Jin; Jiechun Huang; Liewen Pang; Yiqing Wang; Yuming Wu; Xiaotian Sun

doi:10.1371/journal.pone.0283617

Integrative identification of hub genes in development of atrial fibrillation related stroke

PLoS One. 2023 Mar 23;18(3):e0283617. doi: 10.1371/journal.pone.0283617. eCollection 2023.

Authors

Kai Huang¹, Xi Fan¹, Yuwen Jiang¹, Sheng Jin², Jiechun Huang¹, Liewen Pang¹, Yiqing Wang¹, Yuming Wu², Xiaotian Sun¹

Affiliations

¹ Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, China.
² Department of Physiology, Hebei Medical University, Shijiazhuang, China.

Abstract

Background: As the most common arrhythmia, atrial fibrillation (AF) is associated with a significantly increased risk of stroke, which causes high disability and mortality. To date, the underlying mechanism of stroke occurring after AF remains unclear. Herein, we studied hub genes and regulatory pathways involved in AF and secondary stroke and aimed to reveal biomarkers and therapeutic targets of AF-related stroke.

Methods: The GSE79768 and GSE58294 datasets were used to analyze AF- and stroke-related differentially expressed genes (DEGs) to obtain a DEG1 dataset. Weighted correlation network analysis (WGCNA) was used to identify modules associated with AF-related stroke in GSE66724 (DEG2). DEG1 and DEG2 were merged, and hub genes were identified based on protein-protein interaction networks. Gene Ontology terms were used to analyze the enriched pathways. The GSE129409 and GSE70887 were applied to construct a circRNA-miRNA-mRNA network in AF-related stroke. Hub genes were verified in patients using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: We identified 3,132 DEGs in blood samples and 253 DEGs in left atrial specimens. Co-expressed hub genes of EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, and RNF166 were significantly associated with AF-related stroke. The hsa_circ_0018657/hsa-miR-198/EIF4E3 pathway was explored as the regulating axis in AF-related stroke. The qRT-PCR results were consistent with the bioinformatic analysis.

Conclusions: Hub genes EIF4E3, ZNF595, ZNF700, MATR3, ACKR4, ANXA3, SEPSECS-AS1, and RNF166 have potential as novel biomarkers and therapeutic targets in AF-related stroke. The hsa_circ_0018657/hsa-miR-198/EIF4E3 axis could play an important role regulating the development of AF-related stroke.

Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atrial Appendage*
Atrial Fibrillation* / genetics
Computational Biology
Gene Regulatory Networks
Heart Atria
Humans
MicroRNAs* / genetics
Nuclear Matrix-Associated Proteins
RNA-Binding Proteins
Ubiquitin-Protein Ligases

Substances

MicroRNAs
MATR3 protein, human
RNA-Binding Proteins
Nuclear Matrix-Associated Proteins
RNF166 protein, human
Ubiquitin-Protein Ligases
MIRN198 microRNA, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (81601663, 81772042), Shanghai Shen Kang Clinical Research Cultivation Project (SHDC12018X18), and the National Science Foundation of Hebei Province of China (C20200206025). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.