精神分裂症患者外周血中差异表达circRNA、miRNA、mRNA筛选及核心竞争性内源RNA网络构建OACSTPCD

Objective To screen the differentially expressed circRNAs,miRNAs,and mRNAs in the peripheral blood of patients with schizophrenia,to construct a core competitive endogenous RNA(ceRNA)network,and to elucidate the molecular mechanism underlying the development and progression of schizophrenia.Methods Six patients with schizophrenia were included in the schizophrenia group,and four healthy individuals undergoing physical examinations during the same period were included in the healthy control group.Peripheral blood was collected from both groups,and to-tal RNA was extracted to construct cDNA libraries for high-throughput sequencing.R software was used to screen for differ-entially expressed circRNAs,miRNAs,and mRNAs in the peripheral blood of patients with schizophrenia.The miRanda and qTar databases were jointly used to predict circRNA and mRNA interacting with the differentially expressed miRNAs.After intersecting with the differentially expressed circRNA and mRNA,R software was used to construct a network of dif-ferentially expressed ceRNA.The DAVID database was used to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses on the differentially expressed mRNAs in the ceRNA network of pa-tients with schizophrenia.The STRING database was used to construct a protein-protein interaction(PPI)network among the differentially expressed mRNAs in the ceRNA network of patients with schizophrenia.The cytoHubba plugin in Cyto-scape software was used to screen the core mRNAs that influenced the occurrence and development of schizophrenia.MiR-NAs and circRNAs interacting with the core mRNAs were selected to construct a core ceRNA network with differentially ex-pressed genes in the peripheral blood of patients with schizophrenia.Results Compared with the healthy control group,31 circRNAs,213 miRNAs,and 2624 mRNAs were differentially expressed in the peripheral blood of the schizophrenia group.A ceRNA network composed of 5 differentially expressed circRNAs,4 miRNAs,and 57 mRNAs was constructed.The mRNAs in the ceRNA network of patients with schizophrenia were mainly involved in biological processes such as sen-sory perception of chemical stimuli and negative regulation of multicellular organism growth.They were associated with mo-lecular functions such as ubiquitin-ubiquitin ligase activity,guanine nucleotide binding,and enzyme binding,as well as cellular components such as the cytoplasm,actin cytoskeleton,and axon terminus.The mRNAs in the ceRNA network were significantly enriched in metabolic pathways such as NF-κB signaling pathway,PI3K-Akt signaling pathway,Ras sig-naling pathway,and ubiquitin-mediated proteolysis.The PPI network of mRNAs in the differentially expressed ceRNA net-work of patients with schizophrenia included 23 nodes and 22 edges,and two core mRNAs,BRCA1 and GNAS,that influ-enced the occurrence and development of schizophrenia were screened out.The core ceRNA network with differentially ex-pressed genes in the peripheral blood of patients with schizophrenia included 5 nodes and 4 edges.The 5 nodes comprised 2 core mRNAs(BRCA1 and GNAS),1 miRNA(hsa-miR-502-5p),and 2 circRNAs(hsa_circ_0001423 and hsa_circ_0008494).The 4 edges were hsa_circ_0001423/hsa-miR-502-5p/BRCA1,hsa_circ_0001423/hsa-miR-502-5p/GNAS,hsa_circ_0008494/hsa-miR-502-5p/BRCA1,and hsa_circ_0008494/hsa-miR-502-5p/GNAS,respectively.Conclu-sion Compared with healthy controls,31 circRNAs,213 miRNAs,and 2624 mRNAs were differentially expressed in the peripheral blood of patients with schizophrenia,and we constructed the core ceRNA network with 5 nodes and 4 edges.