基于GEO数据库构建精神分裂症miRNA-mRNA调控网络

Exploring the miRNA-mRNA regulatory network in schizophrenia based on GEO database

目的构建miRNA-mRNA调控网络,为探索精神分裂症的分子遗传学发病机制研究提供新的思路。方法于2021年7月在GEO数据库下载精神分裂症外周血miRNA(GSE54578)和死后大脑扣带回mRNA(GSE145554)微阵列数据集,利用GEO2R获取差异表达的miRNA和mRNA,筛选具有靶向mRNA的差异表达miRNA并预测其上游潜在的转录因子;然后,将差异表达miRNA所靶向mRNA与GSE145554数据集所获取的差异表达mRNA取交集基因;最后,对交集基因实施GO和KEGG通路富集分析以揭示它们的生物学功能,构建交集基因PPI网络和miRNA-mRNA调控网络。结果GSE54578共识别出8个上调且具有靶向mRNA的差异表达miRNA,差异表达miRNA共预测出转录因子10个;GSE145554识别出247个下调的差异表达mRNA,取交集基因后筛选出17个目标mRNA;GO分析显示,目标mRNA主要参与星形胶质细胞的分化与发育等,KEGG通路富集分析显示,目标mRNA主要参与Rap1和Ras信号传导通路等,PPI网络分析显示,mRNA(KRAS和CD28)可能是精神分裂症的关键基因。结论基于GEO数据库并整合生物信息学不仅能识别精神分裂症的潜在易感基因,并有助于构建精神分裂症miRNA-mRNA调控网络。

Objective To provide a new idea for exploring the molecular genetic approach to the pathogenesis of schizophrenia via construction of microRNA-messenger RNA(miRNA-mRNA)regulatory network in schizophrenia.Methods The microarray datasets of GSE54578 miRNA expression profiles in peripheral blood and GSE145554 mRNA expression in the anterior cingulate in postmortem brain of schizophrenic subjects were downloaded from Gene Expression Omnibus(GEO)database since July 2021.The GEO2R was used to identify the differentially expressed miRNAs and mRNAs,screen the miRNA with target differentially expressed mRNA,and predict their potential upstream transcription factors.The overlapping genes from the mRNA targeted by the differentially expressed miRNA and the mRNA differentially expressed in GSE 145554 dataset were collected.Then the biological features of hub genes were analyzed via Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and the protein-protein interaction(PPI)network and miRNA-mRNA regulatory network of hub genes were constructed.Results A total of 8 up-regulated differentially expressed miRNA s with targeted mRNA were screened out in GSE54578 datasets regarding schizophrenia,which involved in the regulation of 10 transcription factors,247 down-regulated differentially expressed mRNAs were screened out in GSE145554 datasets,and 17 overlapping mRNAs were obtained.GO analysis showed that the target mRNAs were mainly involved in astrocyte differentiation and development.KEGG pathway enrichment analysis showed that the target mRNAs were mainly involved in Rapl and Ras signaling pathways.PPI network analysis showed that the mRNAs(KRAS and CD28)might be key genes in schizophrenia.Conclusion The integrated bioinformatics analysis based on GEO database can identify potential susceptibility genes in schizophrenia,and it also contributes to the construction of miRNA-mRNA regulatory network in schizophrenia.