Alterations in the Expression Levels of miR-9-5p and miR-4467 in Peripheral Blood of Patients with First-Episode Schizophrenia

Abstract The diagnosis of schizophrenia (SCZ) patients largely rely on abnormal behavior and mental state examination, which is inevitably subjective and susceptible. Finding more stable and objective biomarkers has always been the vision of scholars. In this study, we aim to validate peripheral blood miRNA as potential biomarkers for patients with first-episode schizophrenia (FES). We performed high-throughput sequencing analysis and screened 138 differentially expressed miRNAs (DEmiRNAs) in the peripheral blood in a test cohort (15 FES patients and 15 healthy controls), followed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in miR-9-5p, miR-144-3p, miR-328-3p, and miR-4467 in a validation cohort (35 FES patients and 60 healthy controls), compared with healthy controls, miR-9-5p of FES patients was significantly down-regulated, and miR-4467 was up-regulated. The receiver operating characteristic curve (ROC) demonstrated that miR-4467 had a better diagnostic value than miR-9-5p. Bioinformatics analysis predicted the potential target genes of miR-9-5p and miR-4467 mainly involved in the regulation of body behavior, neuronal differentiation, and nervous system development, and enriched in Neurotrophin, MAPK, and phosphatidylinositol signaling systems. The protein interaction assay identified NEDD4, EIF4G1, FBXL16, FBXL3, etc. as the hub target genes. Summarily, our data suggested the expression of miR-9-5p and miR-4467 in peripheral blood might serve as promising biomarkers for FES patients, and might involve in the occurrence and development of schizophrenia by regulating gene modules related to neurodevelopment and neuroprotective.