The potential effect of miR-۱۷-۵p on RRMS through inhibition of PTEN in CD۴+ T-cells

Backgrounds: Relapsing Remitting Multiple Sclerosis (RRMS) is the most common type ofMultiple sclerosis (MS) which is a chronic autoimmune disease of the central nervous system.Up-regulation of miR-۱۷-۹۲ cluster in lymphocytes contributes to development of autoimmunity.The expression of miR-۱۷-۵p, a member of miR-۱۷-۹۲ cluster increases in CD۴+ T-cells inRRMS patients. The aim of this study was to investigate the target genes of miR-۱۷-۵p in Tcells,the affected pathways and its relationship with RRMS.Materials and Methods: The experimentally validated targets of hsa-miR-۱۷-۵p were obtainedfrom miRTarBase database. The target genes with significant expression in T-cells were selectedthrough DAVID database and their most related pathways were analyzed.Results: Based on the achievements through bioinformatics and KEGG investigation, twosignaling pathways including “T cell receptor signaling pathway” and “Toll-like receptorsignaling pathway” were the most statistically related pathways with targets of miR-۱۷-۵p in Tcells.Conclusion: Information from above signaling pathways indicates that miR-۱۷-۵p may inhibit ۴genes including CD۲۸, MAPK۱, MAP۳K۸ and IRAK۱. It restricts proliferation, differentiation,and immune response, pro-inflammatory, chemotactic and antiviral effects of T-cells. Accordingto previous researches, CD۴+ T-cells are significantly increased in RRMS patients. Upregulationof miR-۱۷-۵p in these cells causes down-regulation of Phosphatase and Tensinhomolog (PTEN), which can lead to autoimmunity. Considering that PTEN is amongexperimentally validated targets of miR-۱۷-۵p, it can be concluded that miR-۱۷-۵p may causesRRMS through inhibiting PTEN instead of its ۴ main targets in CD۴+ T-cells.

کلیدواژه ها:

Multiple sclerosis ، RRMS ، miR-۱۷-۵p ، PTEN ، CD۴+