摘要
目的:探讨阿尔茨海默病(Alzheimer’s disease,AD)与外泌体ceRNA调控网络之间的潜在关系,为临床治疗及研究靶点提供基础。方法:在基因表达综合数据库(gene expression omnibus,GEO)中下载数据,筛选AD患者和健康对照之间的差异基因(differentially expressed genes,DEGs)和差异microRNAs(miRNAs),确定AD的生物标志物。利用DAVID对DEGs进行基因本体论(gene ontology,GO)功能富集分析,用KEGG对DEGs进行信号通路分析,利用cytoscape对DEGs和靶向miRNAs进行作用分析并找出关键节点。结果:筛选到683个DEGs(377个下调的DEGs和306个上调的DEGs),并筛选了90个与AD相关的富集于外泌体和细胞囊泡的DEGs作为我们的目标DEGs。本项目还筛选了748个差异表达的miRNAs(90个下调的miRNAs和658个上调的miRNAs),并筛选出186个细胞外囊泡miRNAs(147个上调的miRNAs和39个下调的miRNAs)。利用数据库预测了这些miRNAs与目标DEGs之间的靶向关系、lncRNA与miRNA之间的靶向关系、circRNA与miRNA之间的靶向关系,构建了lncRNA-miRNA-mRNA和circRNA-miRNA-mRNA ceRNA调控网络,重点探讨了部分结果在AD疾病中的重要作用。结论:这些结果表明,AD的发生是多个相互作用的基因和非编码RNA协同作用的结果。本项目数据的挖掘为AD相关的外泌体ceRNA网络提供了一个新的视角和解析。
Objective:Exploring the potential relationship between Alzheimer’s disease(AD)and exosomal ceRNA regulatory network to provide a basis for clinical treatment and research targets.Methods:Datas were downloaded in the Gene Expression Omnibus database(GEO).Then the differentially expressed genes(DEGs)and differentially expressed miRNAs from AD patients and healthy controls were screened to identify biomarkers of AD.DAVID used to carry out functional enrichment analysis of gene ontology(GO).Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to performed signal pathway analysis on DEGs pathway analysis,Cytoscape was used to construct network between DEGs and differentially expressed miRNAs to identify key node genes.Results:683 DEGs(377 downregulated DEGs and 306 upregulated DEGs)were screened,and 90 AD related DEGs enriched in exosomes and cell vesicles were screened as our target DEGs.The study also screened 748 differentially expressed miRNAs(90 downregulated miRNAs and 658 upregulated miRNAs)and 186 extracellular vesicle miRNAs(147 upregulated miRNAs and 39 downregulated miRNAs).The database was used to predict the targeting relationship between these miRNAs and target DEGs,the targeting relationship between lncRNA and miRNA,and the targeting relationship between circRNA and miRNA.The lncRNAmiRNA-mRNA and circRNA-miRNA-mRNA ceRNA regulatory networks were constructed,and the important role of some results in AD disease was emphatically discussed.Conclusion:These results indicated that the occurrence of AD is the result of the synergistic action of multiple interacting genes and non coding RNAs.The data of this study provides a new perspective and analysis for the exosomal ceRNA network related to AD.
作者
张志清
张永财
刘林轩
李壬清
刘济嘉
杜景考
姜北
魏会平
苏立宁
ZHANG Zhi-qing;ZHANG Yong-cai;LIU Lin-xuan;LI Ren-qing;LIU Ji-jia;DU Jing-kao;JIANG Bei;WEI Huiping;SU Li-ning(Basic Medicine Department,Hebei North University,Zhangjiakou,075000,China)
出处
《神经药理学报》
2022年第4期23-40,共18页
Acta Neuropharmacologica
基金
2021年省级大学生创新创业训练计划项目(No.S202110092003,No.S202110092004)
河北省教育厅青年项目(No.QN2019099)
河北省卫生厅重点科技研究计划(No.20200196)。
