摘要
目的:筛选多发性硬化症(MS)的关键基因,探讨其发病机制并寻找潜在的治疗靶点。方法:从基因芯片数据库(GEO)搜索MS在皮层的基因表达数据,并分析与正常皮层组织的差异表达基因(DEGs);利用DAVID在线软件对挑选出的DEGs进行GO富集分析。基于STRING数据库及Cytoscape软件构建蛋白-蛋白互作(PPI)网络,利用MCODE与Cytohubaa分析其关键基因簇并筛选出有交集的关键基因,最后在动物模型中加以验证。结果:共纳入两套MS基因芯片数据,选出有交集的DEGs 74个,其中上调基因2个,下调基因72个。DEGs GO富集分析发现钾离子跨膜转运等生物学过程与MS的发生发展相关。Cytoscape软件筛选出10个关键基因,从中选出Kcnc1、Kcnc2两个下调基因,并在小鼠EAE模型中得到验证。结论:利用生物信息学方法有效筛选出参与MS发生的Kcnc1、Kcnc2基因,为MS的治疗提供潜在的治疗靶点和策略。
Objective:To screen key genes of multiple sclerosis(MS)and explore its pathogenesis and potential therapeutic targets.Methods:Gene expression data of MS in cortex were searched from the gene chip database(GEO),and differentially expressed genes(DEGs)in MS were identified.DEGs were analyzed by GO enrichment analysis using DAVID tool.A protein-protein interaction(PPI)network was constructed based on STRING database and Cytoscape software,and the key gene clusters were analyzed using MCODE and Cytohubaa,and key genes with intersection were selected and verified in animal models.Results:A total of two sets of MS microarray data were included,and 74 DEGs were selected,with 2 up-regulated genes and 72 down-regulated genes.GO enrichment analysis of DEGs found that biological processes such as potassium ion transmembrane transport were associated with the development of MS.Cytoscape software was screened out 10 key genes,and two down-regulated genes Kcnc1 and Kcnc2 were selected and verified in mice EAE model.Conclusion:Kcnc1 and Kcnc2 genes involved in the occurrence of MS were effectively screened out by bioinformatics method,which provides a potential therapeutic targets and new strategies for treatment of MS.
作者
张贵斌
张闫斌
许涵
朱生东
ZHANG Guibin;ZHANG Yanbin;XU Han;ZHU Shengdong(Gansu Maternal and Child Health Hospital,Lanzhou 730000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第8期1600-1604,共5页
Chinese Journal of Immunology
