Abstract
Objective To screen the dysregulated miRNAs in intracranial aneurysms(IA)by next-generation sequencing and bioinformatics methods,and to explore their possible biological functions.Methods The differentially expressed miRNAs between IA and superficial temporal artery tissues were screened in the public data set numbered GSE66239 in the GEO database.In addition,IA tissues and superficial temporal artery tissues of patients with rupture and hemorrhage of intracranial aneurysm who underwent craniotomy aneurysm clipping in Hongqi Hospital Affiliated to Mudanjiang Medical University from 2021 to 2022 were collected for miRNA sequencing analysis to verify the results of the public data set.The target genes of miRNAs were predicted by miRDB database and miRWalk database.The functional enrichment analysis of miRNA target genes was performed using the R software package clusterProfiler.The protein-protein interaction network(PPI)analysis was performed using the STRING database,and visualized by Cytescape software to extract the core genes in the PPI network.Based on the transcriptome data in the GSE122897 dataset,single-sample gene set enrichment analysis(ssGSEA)was used to evaluate the infiiltration scores of 16 immune cells and 12 immune status scores in the immune.Results In the GSE66239 dataset,54 miRNAs were up-regulated and 1010 miRNAs were down-regulated in IA tissues compared with normal superficial temporal artery tissues.In clinical specimens,compared with normal superficial temporal artery tissue,23 miRNAs were up-regulated and 29 miRNAs were down-regulated in IA tissue.hsa-miR-3176,hsa-miR-1246 and hsa-miR-539-3P showed low expression in IA tissues in GSE66239 dataset and clinical specimens.And 738 and 116 hsa-miR-539-3P-targeted mRNAs were predicted in the miRDB database and the miRWalk database,respectively,and 9 targeted mRNAs were obtained after intersection.Correspondingly,hsa-miR-1246 obtained 407 and 711 targeted mRNAs in the miRDB database and the miRWalk database,respectively,and 34 mRNAs were obtained after intersection.hsa-miR-3176 obtained 482 and 3486 targeted mRNAs in the miRDB database and the miRWalk database,respectively,and 187 mRNAs were obtained after intersection.Functional enrichment analysis showed that the target genes of the above three miRNA were mainly related to the MAPK signaling pathway,FGF pathway,CD8+T cell receptor downstream pathway,S1P pathway,G protein signaling pathway,ERBB signaling pathway,interleukin signaling,neurotransmitter release and other pathways.The PPI network composed of hsa-miR-3176,hsa-miR-1246 and hsa-miR-539-3P target genes contained 121 nodes and 117 interactions.Among them,ERBB4,FGF1,CBL,GNAO1,GNAZ,PTPRT,KCNB1,KCNJ2,POLR2J2 and CD247 are the top 10 core genes in the PPI network,and these core genes were regulated by hsa-miR-3176.Functional enrichment analysis showed that these core genes were related to ERBB signaling pathway,Rap1 signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,CXCR4 signaling pathway,CXCR3 signaling pathway,CD8+T cell receptor signaling pathway and other biological processes.Compared with superficial temporal artery tissue,the infiltration of CD8+T cells,macrophages,mast cells,neutrophils,helper T cells,Thl cells,TIL cells and regulatory T cells in IA increased,APC co-stimulation score,APC co-inhibition score,CCR score,immune examination point score,HLA score,pro-inflammatory score,para-inflammatory score,T cell co-stimulation score,T cell co-inhibition score and type 2 immune response score increased.Correlation analysis showed that core genes were correlated with immune cell infiltration and immune status scores.Conclusion hsa-miR-3176,hsa-miR-1246 and hsa-miR-539-3P are lowly expressed in IA tissues,and their low expression will lead to the occurrence of intracranial aneurysms.关键词
颅内动脉瘤/微小RNA/炎症微环境Key words
Intracranial Aneurysm/microRNA/Inflammatory microenvironment分类
医药卫生
