Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells

microRNA-140-5p 表达与多发性硬化症进展及脑炎性辅助性 T 细胞 1 型分化呈负相关

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作者:Hongbing Guan, Udai P Singh, Roshni Rao, Davit Mrelashvili, Souvik Sen, Haiping Hao, Elizabeth E Zumbrun, Narendra P Singh, Prakash S Nagarkatti, Mitzi Nagarkatti

Abstract

The role of microRNA in the regulation of encephalitogenic T-cell development is of interest in understanding the pathogenesis of multiple sclerosis (MS). Direct binding of microRNAs to their target mRNAs usually suppresses gene expression and facilitates mRNA degradation. In this study, we observed that the expression of several microRNAs was significantly altered in patients with MS. Interestingly, the expression of miR-140-5p, among other microRNAs, was significantly decreased in the peripheral blood mononuclear cells of patients with MS, and this microRNA may regulate encephalitogenic T helper type 1 (Th1) cell differentiation. The expression level of miR-140-5p was inversely correlated with disease severity with greater reduction in relapsing disease compared with remitting disease. Transfection of synthetic miR-140-5p in peripheral blood mononuclear cells suppressed encephalitogenic Th1 differentiation. Signal transducer and activator of transcription 1 (STAT1) was the functional target of miR-140-5p - transfection of the synthetic miR-140-5p suppressed activation of STAT1 and the expression of its downstream target, T-bet. Our results suggested that miR-140-5p is probably involved in the regulation of encephalitogenic T cells in the pathogenesis of MS.

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