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

• Published in: Gene Vol. 544; no. 2; pp. 128 - 133
• Main Authors: Honardoost, Mohammad Amin, Kiani-Esfahani, Abbas, Ghaedi, Kamran, Etemadifar, Masoud, Salehi, Mansoor
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.07.2014
• Subjects: autoimmune diseases; biomarkers; Cell Differentiation - genetics; Cell Differentiation - immunology; Female; Gene Expression Regulation; Genetic Markers; Humans; lymphocytes; Male; MicroRNA; MicroRNAs - genetics; miR-26a; miR-326; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - genetics; myelin sheath; non-coding RNA; pathogenesis; patients; quantitative polymerase chain reaction; Recurrence; relapse; Relapsing–remitting multiple sclerosis; remission; sclerosis; signal transduction; STAT1 Transcription Factor - genetics; Th-17 cells; Th17 Cells - immunology; transforming growth factor beta; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; PP; PR; miRNAs; MS; Th-17 cells; ROC; CNS; DAVID; miR-26a; miR-326; AUC; MicroRNA; hADSCs; Relapsing–remitting multiple sclerosis; KEGG; PBLs; SP
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2014.04.069

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. 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. 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 miR-326 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. 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-silico molecular signaling pathway enrichment analysis detected TGF-β signaling pathway as one of the most statistically relevant pathway with miR-26a targetome. 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 in-silico 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-β signaling pathway (i.e. SMAD4 and SMAD1) and disarrangement of this signaling pathway. •miR-326 is a diagnostic biomarker to discriminate phases of multiple sclerosis.•miR-26a has the same expression pattern as miR-326 in multiple sclerosis.•In-silico analysis showed inducing role of miR-26a in T-helper17 differentiation.