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

Omran Davarinejad,Farnaz Radmehr,Hossein Zhaleh,Reza Heidari Moghadam,Yazdan Rahmati,Mostafa Alikhani,Sajad Najafi,Farzaneh Golmohammadi

doi:10.1007/s12031-021-01945-0

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.

Highlights

Schizophrenia (SCZ) is a chronic debilitating mental disease with a complex identity considered as one of the most mysterious human disorders [1]
A total number of 43 modules were identified for the differentially expressed genes (DEGs) of GSE38485, and only genes of the lightcyan module were selected for the rest of the analysis
It is obvious that Gene Significance (GS) and MM measures are highly correlated, illustrating that genes significantly associated with a trait are often the most important elements of modules associated with the trait (Figure 2c and 3c)

Summary

Introduction

Schizophrenia (SCZ) is a chronic debilitating mental disease with a complex identity considered as one of the most mysterious human disorders [1]. It mainly appears during adulthood primary years affecting both genders, any race, and genetic backgrounds. Diagnosis is made when the clinical manifestations of the disease have appeared and any diagnostic approach to screen the individuals at risk is of special importance. An accumulating evidence suggest familial predisposition as the main risk factor for the disease in addition to other provoking conditions like pregnancy and simultaneous infections, impairments in neurological development and cannabis abuse are other risk factors for SCZ [5]. Development of any molecular diagnostic approach for SCZ requires more detailed unveiling the mechanisms responsible for pathogenesis in the disease

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Conclusion