Identification of diagnostic  microRNAs and their target genes in multiple sclerosis based on interactome  networks using an in silico approach

Azizeh  Asadzadeh; Sara  Esmailzadeh; Fatemeh  Jeldani; Peyman  Naderi; Zahra  Rahmani

doi:10.18502/cjn.v24i2.20682

Azizeh Asadzadeh Department of Biology, School of Sciences, Nour Danesh Institute of Higher Education, Meymeh, Isfahan, Iran
Sara Esmailzadeh Department of Biology, School of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
Fatemeh Jeldani Department of Microbiology, School of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran
Peyman Naderi Department of Biochemistry and Biophysics, School of Advanced Sciences and Technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
Zahra Rahmani Department of Biology, Branch of Sciences, Zand Institute of Higher Education, Shiraz, Iran

DOI: https://doi.org/10.18502/cjn.v24i2.20682

Keywords: MicroRNAs; Multiple Sclerosis; Biomarkers; Gene Expression; Diagnosis

Abstract

Background: The most common demyelinating disease of nerve fibers in the brain and spinal cord is multiple sclerosis (MS) which is associated with several disabilities. By early diagnosis and treatment of MS, the progression of disability can be slowed down. For this purpose, our study aims to identify diagnostic micro ribonucleic acids (miRNAs) and their target genes in MS.

Methods: For the screening of up-regulated and down-regulated genes and miRNAs in patients with MS, GSE17846 (platform: GPL9040, 20 MS samples and 21 control samples), GSE108000 (platform: GPL570, 7 chronic active MS lesions, 8 inactive MS lesions, and 10 controls), and GSE135511 (platform: GPL6883, 20 cases of MS and 10 controls) were extracted from the Gene Expression Omnibus (GEO) database and analyzed based on criteria |log2 (fold change)| > 1 and P-value < 0.05. Protein-protein and miRNA-messenger ribonucleic acid (mRNA) interaction networks were constructed by Cytoscape version 3.9.1 and then, miRNAs and common target genes were detected in MS. Finally, functional enrichment analysis of common target genes was obtained.hsa-miR-574-5p, hsa-miR-1206, hsa-miR-142-3p, hsa-miR-1275, hsa-miR-140-5p, hsa-miR-1207-5p, hsa-miR-613, and hsa-miR-1258 were identified. We also detected 12 target genes for these miRNAs involved in MS. The genes were PLXDC2, Potassium voltage-gated channel subfamily C member 1 (KCNC1), FCGBP, MS4A6A, SNAP25, CCL2, FGF13, GABRG2, SLC5A3, KCNC2, MAL2, and HTR5A.

Conclusion: This research introduces miRNAs and their target genes associated with MS as biomarkers to develop new diagnostic and treatment methods. However, this research can be enhanced by additional validation procedures, such as in vitro and in vivo tests of these discovered biomarkers.