The Effect of Interferon Beta and Natalizumab on miR-20b Expression in Patients with Relapsing-Remitting Multiple Sclerosis is Potentially Mediated by Modulation of the Jak-STAT Signaling Pathway: A Case-control Study

Iran J Immunol. 2024 Jun 30;21(2):158-165. doi: 10.22034/iji.2024.100500.2694. Epub 2024 May 18.

Abstract

Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.

Objective: To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.

Methods: Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.

Results: The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak-STAT signaling pathway is enriched with miR-20b targets (p<0.0001).

Conclusion: Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.

Keywords: Interferon Beta; Multiple Sclerosis; Natalizumab; miR-20b.

MeSH terms

  • Adult
  • Case-Control Studies
  • Computational Biology / methods
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-beta* / therapeutic use
  • Janus Kinases / metabolism
  • Male
  • MicroRNAs* / genetics
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting* / genetics
  • Natalizumab* / therapeutic use
  • STAT Transcription Factors / metabolism
  • Signal Transduction*
  • Young Adult

Substances

  • Interferon-beta
  • Janus Kinases
  • MicroRNAs
  • MIRN20b microRNA, human
  • Natalizumab
  • STAT Transcription Factors