Bioinformatics Analysis of Competing Endogenous RNA Network and Immune Infiltration in Atrial Fibrillation.

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY
Xing Liu, Ke Peng, Guoqiang Zhong, Mingxing Wu, Lei Wang
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引用次数: 3

Abstract

Background: 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.

Methods: 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.

Results: 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 (P < 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.

Conclusion: The findings of our study provide insights into immuno-related ceRNA networks as potential molecular regulators of AF progression.

房颤内源性RNA网络与免疫浸润的生物信息学分析。
背景:目前对房颤(AF)的发病机制尚不清楚。为此,我们采用综合分析方法揭示AF的免疫浸润特征,并研究其与竞争内源性RNA (ceRNA)网络的关系。方法:采用基因表达Omnibus (GEO)的SVA方法整合3个AF mRNA数据集(GSE14975、GSE79768和GSE41177)。结合GEO数据库中的AF circRNA数据集(GSE129409)和miRNA数据集(GSE70887),我们构建了ceRNA网络。然后利用Cytoscape插件cytoHubba从蛋白-蛋白相互作用(PPI)网络中筛选枢纽基因。同时采用CIBERSORT检测免疫浸润,运用Pearson相关系数分析af相关浸润免疫细胞与枢纽基因的相关性。最后,获得了可能与房颤免疫相关的circRNA-miRNA-mRNA调控轴。结果: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,活化树突状细胞和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(P < 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。结论:我们的研究结果为免疫相关的ceRNA网络作为AF进展的潜在分子调节剂提供了见解。
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来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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