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Uncovering the role of microRNAs in response to interferon-beta therapy among multiple sclerosis patients: A
Mitra Pourseirafi1, Seyed Reza Mousavi1, Anoosha Niazmand2
1Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Background:
Multiple sclerosis (MS) is a prevalent neurodegenerative disorder (NDD) affecting young adults. While responses to interferon-beta (IFN-β) 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-β 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-β 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-β-treated RRMS patients and aid in creating more specialized and effective treatment options for MS patients.
Insights
MicroRNAs (miRNAs) significantly impact interferon-beta (IFN-β) treatment response in multiple sclerosis (MS). Identifying these miRNAs could lead to personalized MS therapies.
Area of Science:
- Neuroimmunology
- Genetics
- Pharmacogenomics
Background:
- Multiple sclerosis (MS) is a common neurodegenerative disorder affecting young adults.
- Interferon-beta (IFN-β) is a standard MS treatment, but patient responses vary widely.
- MicroRNAs (miRNAs) are increasingly recognized for their role in immune responses and treatment variability.
Purpose of the Study:
- To systematically review the role of miRNAs in the efficacy, response, and mechanisms of IFN-β therapy in MS patients.
- To identify specific miRNAs associated with IFN-β treatment outcomes in MS.
- To explore the molecular pathways influenced by miRNAs in the context of IFN-β therapy.
Main Methods:
- Systematic review adhering to PRISMA guidelines, searching major databases up to 2025.
- Inclusion of studies on miRNA expression in relapsing-remitting MS (RRMS) patients comparing responders to non-responders.
- Weighted vote-counting synthesis for miRNA significance, followed by target prediction, network construction (miRNA-target, PPI), and pathway enrichment analysis.
Main Results:
- 13 studies analyzed, reporting on over 184 miRNAs related to IFN-β therapy.
- Significantly dysregulated miRNAs identified include miR-29b, miR-504, miR-185-5p, and miR-27a.
- Pathway analysis revealed involvement of miRNAs and hub genes in immune regulation, interferon signaling, and neuroinflammation.
Conclusions:
- Findings highlight miRNA-mediated mechanisms influencing IFN-β treatment in RRMS.
- Identified miRNAs and pathways offer potential for developing targeted and personalized MS treatment strategies.
- This review provides insights into optimizing IFN-β therapy efficacy through a miRNA-centric approach.
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