Zhai Zhenyu, Qi Yiligong, Hu Longlong, Gan Zumao
Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of Medical Intensive Care Unit, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
PLoS One. 2025 Jun 23;20(6):e0324324. doi: 10.1371/journal.pone.0324324. eCollection 2025.
Atrial fibrillation (AF) can lead to substantial morbidity and mortality in clinic. The previous studies demonstrated that miRNAs were closely associated with several cardiovascular diseases, however, the role of miRNAs in the pathogenesis of AF has not been fully elucidated. In order to investigate the important role of miRNA in the mechanisms of AF, we conducted the study through bioinformatics analysis.
We downloaded the miRNA expression profile (GSE68475) and mRNA expression profile (GSE31821) from the Gene Expression Omnibus (GEO) database to explore the differentially expressed miRNAs and mRNAs. The criteria for significant differentially expressed miRNA and mRNA using the R limma package were: adjusted P-value < 0.05, log2fold-change ≥ 1. The target mRNAs related to differentially expressed miRNAs of AF were predicted by using Functional enrichment analysis tool. We Screened overlapped mRNAs based on differentially expressed mRNAs and miRNA related mRNAs using Draw Venn Diagram. GO enrichment analysis and KEGG pathway analysis were conducted to explore the role of miRNAs and mRNAs in the pathogenesis of AF.
A total of 70 differentially expressed miRNAs were screened including 33 up-regulated miRNAs and 34 downregulated miRNAs. All of 94 differentially expressed mRNAs were screened including 56 up-regulated mRNAs and 38 downregulated mRNAs. There were three co-expressed up-regulated differentially expressed genes, including CXCR4, SNAI2, and FHL1. We showed the results of GO functional enrichment analysis and KEGG pathway analysis ranked by enrichment score (-log P value) respectively.
Compared with patients of normal sinus rhythm, miRNA-613 was significantly down-regulated in patients with AF. We demonstrated that SNAI2 and CXCR4 may target genes of miRNA-613 for the first time. Our findings may provide new ideas for clarifying the molecular mechanism of atrial fibrillation.
心房颤动(AF)在临床上可导致严重的发病率和死亡率。先前的研究表明,微小RNA(miRNAs)与多种心血管疾病密切相关,然而,miRNAs在AF发病机制中的作用尚未完全阐明。为了研究miRNA在AF机制中的重要作用,我们通过生物信息学分析进行了本研究。
我们从基因表达综合数据库(GEO)下载了miRNA表达谱(GSE68475)和mRNA表达谱(GSE31821),以探索差异表达的miRNAs和mRNAs。使用R语言的limma包筛选显著差异表达的miRNA和mRNA的标准为:校正P值<0.05,log2倍变化≥1。通过功能富集分析工具预测与AF差异表达miRNAs相关的靶mRNAs。我们使用绘制维恩图基于差异表达的mRNAs和miRNA相关的mRNAs筛选重叠的mRNAs。进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析,以探索miRNAs和mRNAs在AF发病机制中的作用。
共筛选出70个差异表达的miRNAs,包括33个上调的miRNAs和34个下调的miRNAs。共筛选出94个差异表达的mRNAs,包括56个上调的mRNAs和38个下调的mRNAs。有三个共表达的上调差异表达基因,包括趋化因子受体4(CXCR4)、锌指蛋白SNAI2(SNAI2)和四半LIM结构域蛋白1(FHL1)。我们分别展示了按富集分数(-log P值)排序的GO功能富集分析和KEGG通路分析结果。
与正常窦性心律患者相比,AF患者中miRNA-613显著下调。我们首次证明SNAI2和CXCR4可能是miRNA-613的靶基因。我们的发现可能为阐明心房颤动的分子机制提供新的思路。