The fluctuations of expression profiles of critical genes in the miRNA maturation process and pro-and anti-inflammatory cytokines in the pathogenesis and progression of multiple sclerosis.

Abstract

Multiple sclerosis (MS) is a central nervous system disease known for immune-mediated demyelination, inflammatory, and neurodegeneration symptoms. Discovering molecular biomarkers to classify RRMS and SPMS patients, monitor the disease activity, and response to particular treatments is one area that has received notable attraction. MicroRNA (miRNA), a single-stranded non-coding RNA molecule, is a significant regulator of gene expression recruited in pathogenic mechanisms in diverse diseases, especially cancer and MS. Also, the relapsing-remitting features of MS exhibit that both inflammatory and anti-inflammatory cytokines are effective in the progression of the disease over time. It was assessed the expression patterns of the genes (Drosha, Pasha(DGCR8), and Dicer) encoding the critical enzymes in the processing steps of miRNA maturation and major pro-inflammatory and anti-inflammatory cytokines (IFN-α, IFN-β, and IL-6) in blood cells of 40 MS patients (two groups of 10 men and women in both clinical courses of RR and SPMS patients) in comparison with 20 healthy control group (10 males and 10 females). The highest transcription activity of Drosha was observed for RRMS patients (4.2 and 3.6-fold, respectively), and the expression ratio was down regulated in male and female patients with SPMS (3.9- and 3.1-fold, respectively). Considering the studied cytokines, the increase in expression ratio of IL-6 in SPMS patients and the decrease in transcript abundance of INF-α, and INF-β cytokines are consistent with the progression of the disease. Our findings showed that the high and low transcriptional levels of the considered genes seem to be effective in the pathogenesis and progression of MS.