Uncovering the role of microRNAs in response to interferon-beta therapy among multiple sclerosis patients: A systematic review

Abstract

Background: Multiple sclerosis (MS) is a prevalent neurodegenerative disorder (NDD) affecting young adults. While responses to interferon-beta (IFN-(3) vary significantly among patients, it has remained a cornerstone of MS treatment for decades. Increasing evidence suggests that microRNAs (miRNAs) play a crucial role in immune modulation and may influence variations in treatment outcomes. Therefore, this systematic review aims to investigate the role of miRNAs in affecting the therapeutic efficacy, response, and mechanisms of IFN-(3 therapy in patients with MS. Method: This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, and ScienceDirect databases was performed for studies published up to 2025. Studies investigating miRNA expression levels in RRMS patients who were treated/ responded compared to those who were untreated and non-responders were included in this review. A weighted vote-counting synthesis approach was applied to prioritize significantly dysregulated miRNAs based on directional consistency (upregulation/downregulation) and effective sample-size contribution. Subsequently, target prediction performed for miRNAs introduced without targets. Ultimately, miRNA-target network and PPI network constructed and analyzed and pathway enrichment analysis performed. Results: 13 studies were included based on the eligibility criteria, collectively reporting changes in the expression levels of over 184 miRNAs related to IFN-(3 therapy. Significantly dysregulated miRNAs including miR-29b, miR-504, miR-185-5p, and miR-27a were found based on weighted vote-counting synthesis approach. miR-29b-1-5p, miR-193a-3p, miR-346, miR-27a-5p were hub miRNAs come from the miRNA-target interaction network and 10 hub genes came from the PPI network. The results of pathways enrichment analysis indicated that miRNAs and hub genes mainly involved in immune regulation, interferon signaling, and neuroinflammatory mechanisms. Conclusion: These findings could illuminate miRNAs' mediated mechanisms in IFN-(3-treated RRMS patients and aid in creating more specialized and effective treatment options for MS patients.