He Mei,You Xu,Yang Yunbin,Li Yanping,Zhang Lifen,Lu Zixiang,Zhang Yunqiao,Long Qing,Ma Xiao,Zeng Yong,Exploring the miRNA-mRNA regulatory network in schizophrenia based on GEO database[J].SICHUAN MENTAL HEALTH,2022,35(2):120-125
Exploring the miRNA-mRNA regulatory network in schizophrenia based on GEO database
Fund projects:国家自然科学基金项目（项目名称：LncRNA XIST41通过IL-6调控神经炎症影响精神分裂症发病的机制研究，项目编号：81960254）；国家自然科学基金项目（项目名称：LncRNA LINCO1547靶向miR-34c-5p促进IL-1β表达影响精神分裂症发病的机制研究，项目编号：82060257）
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 GSE145554 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 miRNAs 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 Rap1 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.