Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland.
Int J Mol Sci. 2023 Sep 10;24(18):13923. doi: 10.3390/ijms241813923.
Multiple sclerosis is a chronic demyelinating disorder with an unclear etiology. A key role is thought to be played by Th17 cells and microRNAs associated with Th17, such as miR-155, miR-326 and miR-223. The present study compared the methylation and hydroxymethylation levels of CpG sites within promoters of these microRNA between MS patients and controls using PBMCs and analyzed their relationship with microRNA expression. Significant intergroup differences were found between the levels of 5-hmC within the CpG-1 miR-155 promoter and CpG within the miR-326 promoter; in addition, miR-155-5p and miR-223-3p expression was elevated in MS patients. Correlation analysis showed a positive relationship between the level of 5-hmC of CpG-2 in the miR-223 promoter and miR-223-3p level. As it is possible to pharmacologically modulate the level of epigenetic modifications, our findings cast light on the etiology of MS and support the development of more effective therapies.
多发性硬化症是一种病因不明的慢性脱髓鞘疾病。Th17 细胞和与 Th17 相关的 microRNAs（如 miR-155、miR-326 和 miR-223）被认为发挥着关键作用。本研究通过 PBMC 比较了 MS 患者和对照组 microRNA 启动子中 CpG 位点的甲基化和羟甲基化水平，并分析了它们与 microRNA 表达的关系。在 miR-155 启动子的 CpG-1 和 miR-326 启动子的 CpG 内的 5-hmC 水平、miR-155-5p 和 miR-223-3p 的表达水平存在组间差异，miR-155-5p 和 miR-223-3p 的表达水平在 MS 患者中升高。相关性分析显示 miR-223 启动子中 CpG-2 的 5-hmC 水平与 miR-223-3p 水平呈正相关。由于可以通过药理学方法调节表观遗传修饰的水平，因此我们的发现揭示了 MS 的病因，并支持开发更有效的治疗方法。
