Clinical Neuroimmunology, Departments of Biomedicine and Neurology, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
J Immunol Res. 2014;2014:897249. doi: 10.1155/2014/897249. Epub 2014 May 12.
MicroRNAs (miRNAs) are a family of noncoding RNAs that play critical roles in the posttranscriptional regulation of gene expression. Accumulating evidence supports their involvement in the pathogenesis of multiple sclerosis (MS). Here, we compare miR-17 expressions in CD4+ T cells from relapsing-remitting (RR) MS patients treated with natalizumab versus untreated patients. miR-17 was downregulated under natalizumab treatment and upregulated during relapse, therefore supporting a possible role of miR-17 in MS immunopathogenesis. Downregulation of miR-17 was associated with upregulation of PTEN, BIM, E2F1, and p21 target genes. In vitro miR-17 inhibition was associated with upregulation of the same targets and resulted in impaired CD4+ T cell activation and proliferation. We further describe deregulated TGFBR2 expression in untreated patients versus healthy volunteers (HVs) and confirm in vitro the link between miR-17 and TGFBR2 expressions. These findings support an effect of natalizumab on expression of specific miRNA and subsequent expression of genes involved in proliferation and control of the cell cycle.
微小 RNA（miRNAs）是一类非编码 RNA，在基因表达的转录后调控中发挥着关键作用。越来越多的证据表明它们参与了多发性硬化症（MS）的发病机制。在这里，我们比较了接受那他珠单抗治疗和未接受治疗的复发缓解型（RR）MS 患者 CD4+T 细胞中的 miR-17 表达。miR-17 在那他珠单抗治疗下下调，在复发时上调，因此支持 miR-17 在 MS 免疫发病机制中的可能作用。miR-17 的下调与 PTEN、BIM、E2F1 和 p21 靶基因的上调有关。体外 miR-17 抑制与相同靶基因的上调有关，并导致 CD4+T 细胞激活和增殖受损。我们进一步描述了未治疗的患者与健康对照者（HVs）之间 TGFBR2 表达的失调，并在体外证实了 miR-17 和 TGFBR2 表达之间的联系。这些发现支持了那他珠单抗对特定 miRNA 表达的影响，以及随后参与增殖和细胞周期控制的基因表达。
