MiR-574-5P, miR-1827, and miR-4429 as Potential Biomarkers for Schizophrenia

Abstract

Schizophrenia is a severe chronic debilitating disorder with millions of affected individuals. Diagnosis is based on clinical presentations, which are made when the progressive disease has appeared. Early diagnosis may help improve the clinical outcomes and response to treatments. Lack of a reliable molecular diagnostic invokes the identification of novel biomarkers. To elucidate the molecular basis of the disease, in this study we used two mRNA expression arrays, including GSE93987 and GSE38485, and one miRNA array, GSE54914, and meta-analysis was conducted for evaluation of mRNA expression arrays via metaDE package. Using WGCNA package, we performed network analysis for both mRNA expression arrays separately. Then, we constructed protein-protein interaction network for significant modules. Limma package was employed to analyze the miRNA array for identification of dysregulated miRNAs (DEMs). Using genes of significant modules and DEMs, a mRNA-miRNA network was constructed and hub genes and miRNAs were identified. To confirm the dysregulated genes, expression values were evaluated through available datasets including GSE62333, GSE93987, and GSE38485. The ability of the detected hub miRNAs to discriminate schizophrenia from healthy controls was evaluated by assessing the receiver-operating curve. Finally, the expression levels of genes and miRNAs were evaluated in 40 schizophrenia patients compared with healthy controls via Real-Time PCR. The results confirmed dysregulation of hsa-miR-574-5P, hsa-miR-1827, hsa-miR-4429, CREBRF, ARPP19, TGFBR2, and YWHAZ in blood samples of schizophrenia patients. In conclusion, three miRNAs including hsa-miR-574-5P, hsa-miR-1827, and hsa-miR-4429 are suggested as potential biomarkers for diagnosis of schizophrenia.

Keywords: Real-Time PCR; Schizophrenia; WGCNA; metaDE; microRNA.