基于GEO数据库的子痫前期患者血浆外泌体miRNA表达特征分析

Analysis of miRNA expression characteristics of plasma exosomes in patients with preeclampsia based on GEO database

目的 基于基因表达数据库(Gene Expression Omnibus, GEO)分析子痫前期(preeclampsia, PE)患者血浆外泌体miRNA表达特征及调控网络。方法 筛选GEO数据库中PE患者的miRNA表达谱数据。时间截点为2022年12月,筛选条件选择“Preeclampsia”,物种类型选择“Homo sapiens”,获得GSE94721和GSE175807的芯片数据。应用DESeq2分析PE的差异表达miRNA,并对相关通路进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路分析,而后使用蛋白质-蛋白质相互作用(protein-protein interaction, PPI)分析miRNA的靶基因,基于网络拓扑学degree值筛选出关键基因。结果 共筛选出差异miRNA 10个,其中上调5种,下调5种;KEGG分析显示,PE患者有hsa00230嘌呤代谢、hsa00240嘧啶代谢、hsa00562磷酸肌醇代谢等富集信号通路(P<0.05);基因本体论(Gene Ontology, GO)功能分析显示,生物过程(biological process, BP)包括细胞核核糖体大亚基、DNA损伤检查点、细胞有丝分裂G1S周期转变等,细胞组分(cellular components, CC)包括组蛋白脱乙酰酶复合物、组蛋白乙酰转移酶复合物、乙酰转移酶复合体等,分子功能(molecular function, MF)包括脂肪酰辅酶A结合、可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体结合、核苷酸结合等条目;STRING分析发现PE患者外泌体表达的关键miRNA为has-miR-223-3p、has-miR-26a-5p及has-miR-370-3p,排名前10的分别是ZNF608、STOX2、FOXO1、TAOK1、NF1、CDC6、PANK3、UBN2、CDK8及TRPS1。结论 PE患者血浆外泌体表达的关键miRNA为has-miR-223-3p、has-miR-26a-5p及has-miR-370-3p,并可能通过调控ZNF608、STOX2、FOXO1等关键基因参与了PE的疾病进程。

Objective To apply the Gene Expression Omnibus(GEO)database to analyze plasma exosomal miRNA expression characteristics and regulatory networks in patients with preeclampsia(PE).Methods The GEO database was searched and miRNA expression profiles of patients with PE were screened,the data of GSE94721 and GSE175807 were explored,the time cutoff was December 2022,the screening condition was"Preeclampsia",and the species type was"Homo sapiens".DESeq2 was used to analyze the differentially expressed miRNAs in PE,and the related pathways were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and then PPI network were used to identify the key miRNAs,the key regulatory genes were identified by the Degree method in Network Topology.Results Total of 10 differential miRNAs were screened,of which 5 were up-regulated and 5 were down-regulated.KEGG analysis of pathway enrichment showed that patients with PE had hsa00230 Purine metabolism,hsa00240 Pyrimidine metabolism,hsa00562 Phosphatidylinositol metabolism and other enriched signaling pathways(P<0.05);GO functional analysis showed that biological process(BP)included nuclear ribosomal large subunits,DNA damage checkpoints,and cellular mitotic G1S cycle transition,etc,and cellular components(CC)included histone deacetylase complex,histone acetyltransferase complex,acetyltransferase complex,etc,molecular function(MF)includes entries such as fatty acyl-coenzyme A binding,soluble N-ethylmaleimide-sensitive factor attachment protein receptor binding,nucleotide binding and other items;STRING analysis revealed that the key miRNAs expressed by exosomes of patients with PE were has-miR 223-3p,has-miR-26a-5p and has-miR-370-3p,and the top 10 related target genes were ZNF608,STOX2,FOXO1,TAOK1,NF1,CDC6,PANK3,UBN2,CDK8,and TRPS1.Conclusions The key miRNAs expressed in the plasma exosomes of PE patients were has-miR-223-3p,has-miR-26a-5p,and has-miR-370-3p,and may be involved in the disease process of PE through the regulation of key genes such as ZNF608,STOX2,and FOXO1.