miR-326 and miR-26a, two potential markers for diagnosis of relapse and remission phases in patient with relapsing-remitting multiple sclerosis

Background: Multiple sclerosis is an inflammatory autoimmune disease widely characterized by myelin destruction of CNS. Th-17 cells, have been demonstrated to play a crucial role in pathogenesis of MS. MicroRNAs are a new class of non-coding RNAs that participate in post-transcriptional regulation of gene expression. Previous studies have reported a potential role of various miRNAs in induction of Th-17 differentiation and progress of autoimmune diseases. In recent years, it has been shown that miR-326 and miR-26a involved in progress of Th-17 and MS disease. Objective: To evaluate expression pattern of miR-326 and miR-26a in peripheral blood lymphocytes of relapsing remitting MS patients during relapsing and remitting phases compared to healthy control subjects. Materials and methods: Forty RR-MS patients of Isfahan population were diagnosed as relapsing (n = 20) or remitting phase (n = 20) patients according to clinical manifests and expression level of miR-26a and miR326 was measured in these groups by quantitative real time PCR method compared to 20 healthy controls. In-silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-26a by DAVID database to explore possible role of miR-26a in Th17 differentiation. Results: We observed up-regulation of both miR-326 and miR-26a in relapsing phase of multiple sclerosis patients compared with remitting phase (p value = 0.0001) and healthy controls (p value = 0.0091). ROC curve analysis confirmed valuable and precise potential of miR-326 to discriminate between relapsing and remitting phases of multiple sclerosis with specificity and sensitivity of 100% at a proposed optimum cutoff point. Furthermore, in-silica molecular signaling pathway enrichment analysis detected TGF-beta signaling pathway as one of the most statistically relevant pathway with miR-26a targetome. Conclusion: Our results confirmed potential of miR-326 as a diagnostic biomarker to discriminate between relapsing and remitting phases of multiple sclerosis disease. Similar expression pattern to miR-326 and insilico molecular enrichment analysis altogether suggest an inducing role of miR-26a in differentiation of pathogenic Th17 cells during pathogenesis of multiple sclerosis by targeting major components of the TGF-beta signaling pathway (i.e. SMAD4 and SMAD1) and disarrangement of this signaling pathway. (C) 2014 Elsevier B.V. All rights reserved.