Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan 411100, China.
Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Genet Res (Camb). 2022 Jul 16;2022:1415140. doi: 10.1155/2022/1415140. eCollection 2022.
There is still no clear understanding of the pathogenesis of atrial fibrillation (AF). For this purpose, we used integrated analysis to uncover immune infiltration characteristics and investigated their relationship with competing endogenous RNA (ceRNA) network in AF.
Three AF mRNA data sets (GSE14975, GSE79768, and GSE41177) were integrated using the SVA method from Gene Expression Omnibus (GEO). Together with AF circRNA data set (GSE129409) and miRNA data set (GSE70887) from GEO database, we built a ceRNA network. Then hub genes were screened by the Cytoscape plug-in cytoHubba from a protein-protein interaction (PPI) network. As well, CIBERSORT was employed to investigate immune infiltration, followed by Pearson correlation coefficients to unravel the correlation between AF-related infiltrating immune cells and hub genes. Ulteriorly, circRNA-miRNA-mRNA regulatory axises that could be immunologically related to AF were obtained.
Ten hub genes were identified from the constructing PPI network. The immune infiltration analysis revealed that the number of monocytes and neutrophils was higher, as well as the number of dendritic cells activated and T cells regulatory (Tregs) was lower in AF. Seven hub genes (C5AR1, CXCR4, HCK, LAPTM5, MPEG1, TLR8, and TNFSF13B) were associated with those 4 immune cells ( < 0.05). We found that the circ_0005299-miR-1246-C5AR1 and circRNA_0079284-miR-623-HCK/CXCR4 regulatory axises may be associated with the immune mechanism of AF.
The findings of our study provide insights into immuno-related ceRNA networks as potential molecular regulators of AF progression.
心房颤动(AF)的发病机制仍不明确。为此,我们采用整合分析方法揭示免疫浸润特征,并研究其与 AF 竞争内源性 RNA(ceRNA)网络的关系。
从基因表达综合数据库(GEO)中,采用 SVA 方法整合了 3 个 AF mRNA 数据集(GSE14975、GSE79768 和 GSE41177)。同时,从 GEO 数据库中整合了 AF circRNA 数据集(GSE129409)和 miRNA 数据集(GSE70887),构建了 ceRNA 网络。然后,通过 Cytoscape 插件 cytoHubba 从蛋白质-蛋白质相互作用(PPI)网络中筛选出枢纽基因。同时,采用 CIBERSORT 分析免疫浸润情况,并通过 Pearson 相关系数揭示与 AF 相关浸润免疫细胞和枢纽基因之间的相关性。此外,获得了可能与 AF 免疫相关的 circRNA-miRNA-mRNA 调控轴。
从构建的 PPI 网络中鉴定出 10 个枢纽基因。免疫浸润分析显示,AF 中单核细胞和中性粒细胞数量增加,而树突状细胞激活和 T 细胞调节(Tregs)数量减少。7 个枢纽基因(C5AR1、CXCR4、HCK、LAPTM5、MPEG1、TLR8 和 TNFSF13B)与这 4 种免疫细胞相关(<0.05)。我们发现,circ_0005299-miR-1246-C5AR1 和 circRNA_0079284-miR-623-HCK/CXCR4 调控轴可能与 AF 的免疫机制有关。
本研究结果为免疫相关 ceRNA 网络作为 AF 进展的潜在分子调节剂提供了新的见解。