基于生物信息学的系统性硬化症潜在miRNA-mRNA调控网络的构建

Construction of a potential miRNA-mRNA regulatory network in systemic sclerosis based on bioinformatics

目的基于生物信息学分析构建系统性硬化症(SSc)潜在的微RNA(miRNA)-mRNA调控网络。方法使用GEO2R工具对基因表达图谱(GEO)数据库进行分析,筛选出SSc患者和正常健康者之间的差异表达miRNA(DEM)。通过miRNet网站检索DEM靶基因,FunRich软件分析靶基因的转录因子,利用DAVID在线分析工具对靶标基因进行基因本体(GO)注释和京都基因与基因组数据库(KEGG)通路富集分析。STRING数据库和Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络和DEM-Hub基因调控网络,利用GSE146093数据集评估和验证Hub基因的表达。结果筛选出26个DEM,其中2个上调,24个下调。共检索出5450个靶基因,这些靶基因主要富集于P53信号通路、FOXO信号通路、DNA转录和细胞间黏附等,借助FunRich分析发现SP1和YY1为这些靶基因的主要转录因子。通过构建DEM-Hub基因网络发现,大部分Hub基因可能受到miR-455-3p、let-7e-5p和miR-149-5p的调控。GSE146093数据集中UTP15、PTBP1的表达一致。因此推测let-7e-5p-UTP15、miR-4440-PTBP1是潜在的调控靶点。结论构建了SSc潜在的miRNA-mRNA调控网络,即let-7e-5p-UTP15、miR-4440-PTBP1是潜在的调控靶点。

Objective To construct a potential microRNA(miRNA)-mRNA regulatory network in systemic sclerosis(SSc)based on bioinformatics.Methods Gene Expression Omnibus(GEO)database was analyzed using GEO2R to screen out the differentially expression miRNA(DEM)between SSc patients and healthy participants.Target genes of DEM were retrieved through the miRNet website,and FunRich software was used to analyze the transcription factors of the target genes.DAVID online analysis tool was used for Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Protein-protein interaction and DEM-Hub gene regulation networks were constructed using the STRING database and Cytoscape software.The expressions of Hub genes were evaluated and verified using GSE146093 dataset.Results Twenty-six DEM were screened,of which 2 were up-regulated and 24 were down-regulated.A total of 5450 target genes were retrieved and were mainly enriched in the P53 and FOXO signaling pathways,DNA transcription and intercellular adhesion,etc.Using FunRich analysis,SP1 and YY1 were found to be the main transcription factors of these target genes.Through constructing the DEM-Hub gene network,it was found that most Hub genes may be regulated by miR-455-3p,let-7e-5p,and miR-149-5p,and UTP15 and PTBP1 were expressed in a similar way in the GSE146093 dataset.Conclusion The potential miRNA-mRNA regulatory network of SSc was constructed,namely let-7e-5p-UTP15 and miR-4440-PTBP1,which are presumed to be potential regulatory targets.