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

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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.

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The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This article is the result of the findings of the research project 97542 that was approved and financed by Vice Chancellor for Research and Research and Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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Authors and Affiliations

  1. Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Omran Davarinejad, Farzaneh Golmohammadi, Farnaz Radmehr, Mostafa Alikhani & Yazdan Rahmati

  2. Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sajad Najafi

  3. Substance Abuse Prevention Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Hossein Zhaleh

  4. Cardiovascular Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Reza Heidari Moghadam

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  1. Omran Davarinejad
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  2. Sajad Najafi
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  3. Hossein Zhaleh
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  4. Farzaneh Golmohammadi
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  5. Farnaz Radmehr
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  6. Mostafa Alikhani
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  7. Reza Heidari Moghadam
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  8. Yazdan Rahmati
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Contributions

Conceptualization: Yazdan Rahmati and Omran Davarinejad; computational analyses and experiments: Yazdan Rahmati, Sajad Najafi, and Hossein Zhaleh; writing manuscript: Yazdan Rahmati, Sajad Najafi, Farzaneh Golmohammadia, Farnaz Radmehra, Mostafa Alikhania, and Reza Heidari Moghadam; and supervision and finalization: Yazdan Rahmati.

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Correspondence to Yazdan Rahmati.

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All patients gave their signed written informed consent letters. Medical Research and Ethical Committee of Kermanshah University of Medical Sciences (Kermanshah, Iran; registration no. IR.KUMS.REC.1397.490; grant number 97542) approved the study performed under ethical principles contained in the 7th and current (2013) editions of Helsinki Declaration.

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Davarinejad, O., Najafi, S., Zhaleh, H. et al. MiR-574-5P, miR-1827, and miR-4429 as Potential Biomarkers for Schizophrenia. J Mol Neurosci 72, 226–238 (2022). https://doi.org/10.1007/s12031-021-01945-0

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