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

Abstract

Dysregulation of microRNA expression has been shown in multiple sclerosis (MS); however, the mechanisms underlying these changes, their response to therapy and the impact of microRNA changes in MS are not completely understood. Dicer mediates the cleavage of precursor microRNAs to mature microRNAs and is dysregulated in multiple pathologies. Having shown that interferons regulate Dicer in vitro, we hypothesized that MS patient IFNS1 a treatment could potentially alter Dicer expression. Dicer mRNA and protein levels, as well as microRNA expression, were determined in MS patient and healthy control PBL. Acute responses to IFNS1 a were assessed in 50 patients. We found that Dicer protein but not mRNA levels decreases in MS patients while both are selectively induced in patients responding well to IFNS1 a. Potential microRNA biomarkers for relapsing remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and IFNSla response are described. Contrasts in Dicer and microRNA expression levels between patient populations may offer insight into mechanisms underlying disease courses and responses to IFN1S1a therapy. This work identifies Dicer regulation as both a potential mediator of MS pathology and a therapeutic target.