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

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. Results: 9 diagnostic miRNAs, including hsa-miR-107, 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.