Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia.
PLoS One. 2010 Aug 11;5(8):e12132. doi: 10.1371/journal.pone.0012132.
It is well established that Multiple Sclerosis (MS) is an immune mediated disease. Little is known about what drives the differential control of the immune system in MS patients compared to unaffected individuals. MicroRNAs (miRNAs) are small non-coding nucleic acids that are involved in the control of gene expression. Their potential role in T cell activation and neurodegenerative disease has recently been recognised and they are therefore excellent candidates for further studies in MS. We investigated the transcriptome of currently known miRNAs using miRNA microarray analysis in peripheral blood samples of 59 treatment naïve MS patients and 37 controls. Of these 59, 18 had a primary progressive, 17 a secondary progressive and 24 a relapsing remitting disease course. In all MS subtypes miR-17 and miR-20a were significantly under-expressed in MS, confirmed by RT-PCR. We demonstrate that these miRNAs modulate T cell activation genes in a knock-in and knock-down T cell model. The same T cell activation genes are also up-regulated in MS whole blood mRNA, suggesting these miRNAs or their analogues may provide useful targets for new therapeutic approaches.
多发性硬化症（MS）是一种免疫介导的疾病，这一点已得到充分证实。目前尚不清楚是什么导致 MS 患者的免疫系统受到控制，而未受影响的个体则不受控制。微小 RNA（miRNA）是一种参与基因表达调控的小型非编码核酸。最近已经认识到它们在 T 细胞激活和神经退行性疾病中的潜在作用，因此它们是 MS 进一步研究的优秀候选者。我们使用 miRNA 微阵列分析对 59 名未经治疗的 MS 患者和 37 名对照的外周血样本进行了目前已知 miRNA 的转录组分析。在这 59 名患者中，18 名患者为原发性进行性，17 名患者为继发性进行性，24 名患者为复发缓解性疾病。在所有 MS 亚型中，miR-17 和 miR-20a 在 MS 中均显著低表达，通过 RT-PCR 得到证实。我们证明这些 miRNA 在敲入和敲低 T 细胞模型中调节 T 细胞激活基因。在 MS 全血 mRNA 中也上调了相同的 T 细胞激活基因，表明这些 miRNA 或其类似物可能为新的治疗方法提供有用的靶点。
