• Down-regulation of MBP in MAPK signaling pathway by miR-15a-3p might promote the multiple sclerosis status: high-throughput bioinformatics investigation
  • Ali Sinaei Esfahani,1 Mohammad Rezaei,2 Mansoureh Azadeh,3,*
    1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    3. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran


  • Introduction: Due to a better understanding of the mechanisms behind relapsing-remitting multiple sclerosis, various disease-modifying drugs have been produced during the past several decades through immune system control or suppression. However, the options for treating progressive multiple sclerosis are still largely unsatisfactory and challenging [1]. We used high-throughput data analysis in this research to identify new regulatory RNAs (both protein-coding and non-coding) in MS patients.
  • Methods: To identify novel potential dysregulated regulatory mRNAs in MS patients relative to controls, the GSE38010 [2] microarray dataset was downloaded and analyzed. Affy package [3] obtained the raw data from Bioconductor (http://bioconductor.org/). The limma software was used to normalize the raw data and analyze differential expression (DE) [4]. The Enrichr [5] online database (https://maayanlab.cloud/Enrichr/) was used for pathway enrichment and gene ontology (GO) analysis. To identify new regulatory miRNAs for possibly dysregulated mRNAs, an investigation of microRNA (miRNA)-mRNA interactions was carried out using the online tool miRWalk [6] (http://mirwalk.umm.uni-heidelberg.de/).
  • Results: Based on high-throughput microarray data analysis, the MBP gene has a significantly low expression in the MS samples (logFC: -6.465, adj. P. Val: 0.010899). miRNA-mRNA interaction by mirwalk revealed that hsa-miR-15a-3p regulates the expression of the MBP gene (score: 1, binding energy: -23, number of pairings: 18) by maintaining an RNA interaction by the seed region in the 3’UTR of MBP mRNA. Based on Enrichr, MBP regulates the Neural crest differentiation and MAPK signaling pathways. Positive regulation of metallopeptidase activity (GO:1905050) and positive regulation of chemokine (C-X-C motif) ligand two production (GO:2000343) are the two main biological processes regulated by MBP.
  • Conclusion: By suppressing the expression of MBP, miR-15a-3p regulates the Neural crest differentiation and MAPK signaling pathways by involving the positive regulation of metallopeptidase activity. MBP is a significant low-expressed mRNA in MS patients. So, miR-15a-3p could promote MS by playing a role in the low-expression of MBP.
  • Keywords: Microarray analysis, Systems biology, Multiple Sclerosis, RNA interaction network