• miR-17-5p might regulate the expression level of RXFP1 in the Neuroactive ligand-receptor interaction pathway in the multiple sclerosis patients: integrated systems biology approach
  • 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: Through immune system regulation or suppression, several disease-modifying medications have been developed during the past several decades due to more excellent knowledge of the processes behind relapsing-remitting multiple sclerosis. However, the treatment choices for progressive multiple sclerosis are still mostly unsatisfactory and challenging [1]. In this study, we performed a high-throughput data analysis to find the novel regulatory RNAs (protein-coding and non-coding) in multiple sclerosis (MS) patients.
  • Methods: The GSE38010 [2] microarray dataset was downloaded and analyzed to find novel possible dysregulated regulatory mRNAs in the MS patients compared to control. Raw data was downloaded by affy package [3], downloaded from Bioconductor (http://bioconductor.org/). Normalization of raw data and differential expression (DE) analysis were performed by the limma package [4]. Pathway enrichment and gene ontology (GO) analysis were performed by Enrichr [5] online database (https://maayanlab.cloud/Enrichr/). microRNA (miRNA)-mRNA interaction analysis was performed by miRWalk [6] online software to find novel regulatory miRNAs for potentially dysregulated mRNAs (http://mirwalk.umm.uni-heidelberg.de/).
  • Results: Based on microarray analysis, RXFP1 has a significant up-regulation in the MS patients compared to control samples (logFC: 6.31551, adj. P. Val: 0.00991). miRWalk analysis revealed that hsa-miR-17-5p has significant high-score interaction with RXFP1 (score: 1, position: 3’UTR, number of pairings: 16, binding energy: -20.5). Based on Enrichr pathway analysis, RXFP1 plays a significant role in the Relaxin signaling pathway and Neuroactive ligand-receptor interaction pathway. Based on GO analysis, RXFP1 regulates the activation of adenylate cyclase activity (GO:0007190), is involved in G protein-coupled peptide receptor activity (GO:0008528), and is located integral component of the plasma membrane (GO:0005887).
  • Conclusion: Based on this integrated systems biology research, hsa-miR-17-5p regulates the Relaxin signaling pathway and Neuroactive ligand-receptor interaction pathway by activating adenylate cyclase activity involved in G protein-coupled peptide receptor activity in MS patients. This miRNA performed mentioned mechanism by regulating the expression level of RXFP1 mRNA. Disturbance of the interaction between miR-17-5p and RXFP1 might be one of the possible causes of MS.
  • Keywords: Microarray analysis, Systems biology, Multiple Sclerosis, RNA interaction network