Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran.
MS Research Center, Neuroscience Institute, Tehran University of Medical Science, Tehran, Iran.
Neuromolecular Med. 2020 Mar;22(1):100-110. doi: 10.1007/s12017-019-08567-1. Epub 2019 Sep 3.
The hallmark of multiple sclerosis (MS) pathogenesis is the breakdown of peripheral tolerance in the immune system. However, its molecular mechanism is not completely understood. Since long non-coding RNAs (lncRNAs) has played important roles in regulation of immunological pathways, here, we evaluated the expression of a novel lncRNA, TOB1-AS1, and its putative associated coding genes in the mechanism of maintaining immune tolerance in peripheral blood of MS patients to assess their possible roles in MS pathogenesis. In this study, 39 MS patients and 32 healthy matched controls were recruited. Real-time PCR standard curve method was used to quantify transcript levels of TOB1-AS1, TOB1, SKP2, and TSG. In addition, the potential sex hormone receptor binding sites on target genes promoter were analyzed using JASPR software. This work demonstrates a negative correlation between TOB1-AS1 expression and EDSS of patients. Also, a robust dysregulation of co-expression of TOB1-AS1 lncRNA and the coding genes in MS patients compared to controls was observed. Such dysregulation in this pathway may be related to MS pathogenesis and response to interferon treatment.
多发性硬化症（MS）发病机制的标志是免疫系统外周耐受的破坏。然而，其分子机制尚不完全清楚。由于长非编码 RNA（lncRNA）在免疫途径的调节中发挥着重要作用，在这里，我们评估了一种新型 lncRNA，即 TOB1-AS1，及其潜在相关编码基因在 MS 患者外周血维持免疫耐受机制中的表达，以评估它们在 MS 发病机制中的可能作用。在这项研究中，招募了 39 名 MS 患者和 32 名健康匹配对照者。实时 PCR 标准曲线法用于定量 TOB1-AS1、TOB1、SKP2 和 TSG 的转录水平。此外，使用 JASPR 软件分析了靶基因启动子上潜在的性激素受体结合位点。这项工作表明，TOB1-AS1 表达与患者的 EDSS 呈负相关。此外，与对照组相比，MS 患者中 TOB1-AS1 lncRNA 和编码基因的共表达表现出明显的失调。该通路的这种失调可能与 MS 的发病机制和对干扰素治疗的反应有关。
