miR-145 and miR20a-5p Potentially Mediate Pleiotropic Effects of Interferon-Beta Through Mitogen-Activated Protein Kinase Signaling Pathway in Multiple Sclerosis Patients

Area of Science:

• Neuroimmunology
• Molecular Biology
• Biomarker Discovery

Background:

• MicroRNAs (miRNAs) are implicated in the immunopathogenesis of multiple sclerosis (MS).
• The precise mechanism of action for interferon beta (IFN-β) in relapsing-remitting MS (RRMS) remains unclear.
• miR-145 and miR-20a-5p have been identified as diagnostic biomarkers in treatment-naïve RRMS patients.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying IFN-β therapy in RRMS.
• To evaluate miR-145 and miR-20a-5p as potential biomarkers for monitoring IFN-β treatment response.
• To investigate the role of miRNAs in IFN-β signaling pathways, including JAK/STAT and MAPK.

Main Methods:

• Expression analysis of miR-145 and miR-20a-5p in blood samples from treatment-naïve RRMS patients, IFN-β-treated RRMS patients, and healthy volunteers.
• In silico molecular signaling pathway enrichment analysis of validated and predicted miRNA targets.
• Receiver Operating Characteristic (ROC) curve analysis for miR-145 as a potential therapeutic response biomarker.

Main Results:

• Expression levels of miR-145 and miR-20a-5p were normalized in IFN-β-treated RRMS patients compared to treatment-naïve patients.
• Mitogen-activated protein kinase (MAPK) pathway was identified as a significantly enriched pathway associated with miR-145 and miR-20a-5p targets.
• ROC curve analysis demonstrated that miR-145 holds potential for monitoring therapeutic response to IFN-β.

Conclusions:

• Restoration of miR-145 and miR-20a-5p expression in IFN-β-treated patients suggests that miRNAs mediate the pleiotropic effects of IFN-β.
• The enrichment of the MAPK pathway highlights the significance of non-canonical pathways in IFN-β signaling.
• miR-145 shows promise as a biomarker for assessing treatment efficacy in RRMS patients receiving IFN-β therapy.