microRNA⁃223在动脉粥样硬化发生过程中的网络调控机制

The network regulation mechanism of microRNA⁃223 in the development of atherosclerosis

microRNA⁃223(miR⁃223)是参与动脉粥样硬化(atherosclerosis,AS)炎性调控、细胞生长等通路的微小非编码RNA。本研究系统地探究miR⁃223及其靶基因的网络调控机制,以便全面理解miR⁃223在AS中的作用。利用miRNA靶基因预测数据库miRDB、miRmap、TargetScan和miRTarBase获取miR⁃223的靶基因集。R语言分析基因表达综合数据库(gene expression omnibus,GEO)共享平台动脉粥样硬化斑块差异表达基因集(GSE100927),筛选出斑块差异表达基因,并与miR⁃223靶基因集交叉匹配。利用基因本体(gene ontology,GO)及基因组数据库(kyoto encyclopedia of genes and genomes,KEGG)分析研究差异表达基因功能。结果显示,斑块中下调的1584个差异表达基因与miR⁃223靶基因交叉匹配得到422个交集mRNA。GO及KEGG富集分析发现miR⁃223可能通过细胞生长、炎症反应以及血管平滑肌收缩等信号通路调节动脉粥样硬化斑块的发生发展过程。蛋白相互作用网络(protein⁃protein interaction networks,PPI)分析获得关键节点基因是INADL、JAM3、SMTN、LDB3、YAP1、TJP1、NCKAP1、PDLIM3、MICAL2和MPP5,其中YAP1也与铜死亡相关。我们还发现miR⁃223可能直接靶向GLS、GCSH调控铜死亡,参与动脉粥样硬化的发生发展过程。本研究表明,miR⁃223主要通过调控细胞生长、铜死亡等相关信号通路影响动脉粥样硬化的各个进程。

microRNA⁃223(miR⁃223)is a small non⁃coding RNA involved in the inflammatory regulation and cell growth pathways of atherosclerosis(AS).In this study,we systematically explored the network regulatory mechanisms of miR⁃223 and its target genes in order to fully understand the role of miR⁃223 in AS.The target gene set of miR⁃223 was obtained by miRDB,miRmap,TargetScan and miRTarBase.The plaque differential expression gene set(GSE100927),shared platform of gene expression omnibus(GEO)database,was analyzed by R language,and the plaque differential expression genes were screened out and cross⁃matched with the miR⁃223 target genes.The functions of differentially expressed genes were analyzed using the gene ontology(GO)and the kyoto encyclopedia of genes and ge⁃nomes(KEGG).A total of 1584 differentially expressed genes which were downregulated in plaques were cross⁃matched with miR⁃223 target genes to yield 422 intersectional mRNAs.GO and KEGG enrichment analysis showed that miR⁃223 may regulate the occurrence and development of atherosclerotic plaques through signaling pathways such as cell growth,inflammatory response and vascular smooth muscle contraction.Protein⁃protein interaction networks(PPI)analysis revealed that the key node genes were INADL、JAM3、SMTN、LDB3、YAP1、TJP1、NCKAP1、PDLIM3、MICAL2 and MPP5.YAP1 was also associated with cuproptosis.We also found that miR⁃223 may directly target GLS and GCSH to regulate cuproptosis and participate in the occurrence and development process of AS.