心房颤动中ceRNA免疫调节网络及组织浸润免疫细胞的构建与综合分析
The Construction and Comprehensive Analysis of a ceRNA Immunoregulatory Network and Tissue-Infiltrating Immune Cells in Atrial Fibrillation.
作者信息
Liu Xing, Zhong Guoqiang, Li Wenbin, Zeng Yiqian, Wu Mingxing
机构信息
Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, People's Republic of China.
Department of Cardiology, Guangxi Cardiovascular Institute, The First Affiliated Hospital of Guangxi Medical University, Guangxi, People's Republic of China.
出版信息
Int J Gen Med. 2021 Nov 30;14:9051-9066. doi: 10.2147/IJGM.S338797. eCollection 2021.
BACKGROUND
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.
背景
目前，心房颤动（AF）发病机制仍不清楚。我们构建了一个ceRNA免疫调节网络以进一步了解AF的机制。
方法
通过SVA方法整合来自基因表达综合数据库（GEO）的四个AF mRNA数据集。通过将ImmPort数据库与通过加权基因共表达网络分析（WGCNA）获得的与AF最相关模块中的基因相结合，筛选出AF相关免疫基因（AF-IRGs）。然后，从GEO数据库中提取circRNA和miRNA表达，并与相关数据库进行映射。接下来，构建免疫相关的circRNA-miRNA-mRNA ceRNA网络，并从蛋白质-蛋白质相互作用（PPI）网络中筛选出枢纽基因，并进一步筛选AF中差异表达（DE）的枢纽基因。此外，使用CIBERSORT研究AF中的免疫浸润。随后，使用Pearson相关系数分析DE枢纽基因与AF相关浸润免疫细胞之间的关系。最终，构建了AF中免疫细胞相关的ceRNA子网。
结果
共检测到95个AF-IRGs，并构建了一个包含12个circRNA、7个miRNA和50个mRNA的AF免疫相关ceRNA网络。免疫浸润分析表明，AF中中性粒细胞水平较高，而调节性T细胞（Tregs）和活化的自然杀伤细胞（NK细胞）水平较低。四个DE枢纽基因（CXCL12、IL7R、TNFSF13B、CD8A）与Tregs或活化的NK细胞免疫细胞相关（P<0.05）。最终在AF中构建了包括5个circRNA（has_circ_0001190、has_circ_0006725、has_circ_0079284、has_circ_0005299和has_circ_0002103）、4个miRNA（has-miR-198、has-miR-623、has-miR-1246和has-miR-339-3p）和4个DE枢纽基因的Tregs或活化的NK细胞免疫细胞相关ceRNA子网。
结论
我们的结果从免疫相关ceRNA网络的角度为AF进展的分子机制提供了新的见解。
Zotero 插件