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Dicer and microRNA expression in multiple sclerosis and response to interferon therapy

William J Magner1, Bianca Weinstock-Guttman2, Mina Rho3

  • 1Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA; Department of Microbiology and Immunology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA.

Journal of Neuroimmunology
|March 6, 2016
PubMed

Insights

Multiple sclerosis (MS) involves microRNA changes, with Dicer protein levels decreasing in patients. Interferon beta-1a (IFNβ1a) therapy selectively increases Dicer and microRNA levels in responders, suggesting Dicer as a therapeutic target for MS.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNA (miRNA) dysregulation is implicated in multiple sclerosis (MS) pathogenesis, but underlying mechanisms and therapeutic impacts remain unclear.
  • Dicer, an enzyme crucial for mature miRNA biogenesis, is dysregulated in various diseases and its role in MS requires further investigation.
  • Interferons (IFNs) are known to regulate Dicer in vitro, prompting investigation into their effect on Dicer expression in MS patients.

Purpose of the Study:

  • To investigate the effect of interferon beta-1a (IFNβ1a) treatment on Dicer expression and miRNA profiles in patients with multiple sclerosis.
  • To identify potential miRNA biomarkers associated with different MS subtypes and response to IFNβ1a therapy.

Main Methods:

  • Dicer mRNA and protein levels, along with miRNA expression, were quantified in peripheral blood lymphocytes (PBL) from MS patients and healthy controls.
  • Acute responses to IFNβ1a were assessed in a cohort of 50 MS patients.

Main Results:

  • Dicer protein levels were decreased in MS patients compared to controls, while mRNA levels showed no significant difference.
  • IFNβ1a treatment selectively induced both Dicer mRNA and protein levels in patients who responded well to the therapy.
  • Distinct miRNA expression profiles were identified, potentially serving as biomarkers for relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and IFNβ1a response.

Conclusions:

  • Dicer dysregulation, particularly decreased protein levels, is associated with MS pathology.
  • IFNβ1a therapy can modulate Dicer and miRNA expression in MS patients, highlighting Dicer as a potential therapeutic target.
  • Identified miRNA signatures may offer insights into MS disease mechanisms and predict treatment response.
Keywords:
BiomarkersDicerInterferonMicroRNAMultiple sclerosisTherapy

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