title: miR-145 and miR20a-5p Potentially Mediate Pleiotropic Effects of Interferon-Beta Through Mitogen-Activated Protein Kinase Signaling Pathway in Multiple Sclerosis Patients.
abstract: MicroRNAs (miRNAs) are crucial to the immunopathogenesis of multiple sclerosis (MS). The mechanism of action of interferon beta (IFN-β) in relapsing-remitting (RR) MS patients is largely unknown. miR-145 and miR-20a-5p previously reported as diagnosis biomarker in treatment naïve RRMS patients and their expression after IFN-β therapy might be indicative of molecular mechanism of IFN-β. Cross-talking between JAK/STAT pathway and complementary pathways like MAPK is important in IFN-β signaling. Here, in order to clarify the ambiguous molecular mechanism of IFN-β and evaluate the potential use of them as a biomarker for monitoring of therapy, we investigated the expression of miR-145 and miR-20a-5p in blood sample of 15 treatment naïve RRMS patients, 15 IFN-β-treated RRMS patients, and 15 healthy volunteers (HVs). In silico molecular signaling pathway enrichment analysis was fulfilled on validated and predicted targets of miR-145 and miR-20a-5p to probe the plausible role of them on molecular effects of IFN-β. We identified miR-145 and miR-20a-5p level was normalized in IFN-β-treated patients, and MAPK pathway was one of the most relevant pathways that recognized by molecular signaling pathway enrichment analysis. Moreover, ROC curve analysis of miR-145 indicated that this miRNA could be used for monitoring of response to IFN-β therapy. Restoration of miR-145 and miR-20a expression in IFN-β-treated patients suggests that pleiotropic effects of IFN-β might be through miRNAs. Enrichment of MAPK pathway underscores the importance of non-canonical pathways in IFN-β signaling.
authors.affiliation: Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Naeim
authors.initials: N
authors.lastname: Ehtesham
authors.affiliation: Neurology Department, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Khorvash
authors.affiliation: Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. mkheirollahi@med.mui.ac.ir.
authors.forename: Majid
authors.initials: M
authors.lastname: Kheirollahi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D058685:Genetic Pleiotropy; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000188:drug therapy / Q000235:genetics
chemical_list: D015415:Biomarkers; C541010:MIRN145 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D016899:Interferon-beta
keywords: Interferon-beta; MAPK pathway; MicroRNA; Multiple sclerosis