Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Neurology, Hamadan University of Medical Sciences, Hamadan, Iran.
J Mol Neurosci. 2020 Aug;70(8):1274-1281. doi: 10.1007/s12031-020-01537-4. Epub 2020 Mar 25.
Fingolimod is an immunotherapeutic drug approved in certain countries as first-line therapy for relapsing-remitting multiple sclerosis (RRMS). The drug has been shown to alter the expression of several coding and non-coding genes. In the current study, we assessed the expression of miR-506-3p, miR-217, miR-381-3p, miR-1827, miR-449a and miR-655-3p in peripheral blood of patients with RRMS undergoing treatment with fingolimod compared with healthy controls. We also compared the expression of these miRNAs between fingolimod responders and non-responders to determine their relevance with regard to response to fingolimod. Expression of miR-381-3p was significantly higher in responders than in controls (RE difference = 3.903, P = 0.005), while expression of miR-655-3p was significantly lower in both responders and non-responders compared with controls (RE difference = -1.03, P = 0.014; RE difference = -1.41, P < 0.0001, respectively). No difference was found in the expression of other miRNAs between study subgroups. In addition, there was no significant difference in the expression of any miRNA between responders and non-responders. Although there were significant pairwise correlations between expression levels of all of the assessed miRNAs in controls, MS patients exhibited differences in correlation patterns. Expression of miR-381-3p was correlated with age in responders. However, expression of other miRNAs did not correlate with age in any study subgroup. The current study indicates a possible role for miR-655-3p and miR-381-3p in the pathogenesis of MS or possible effects of fingolimod on the expression of these miRNAs. Future studies are needed to verify these results in larger patient populations.
芬戈莫德是一种免疫治疗药物，在某些国家被批准作为复发缓解型多发性硬化症（RRMS）的一线治疗药物。该药物已被证明能改变几种编码和非编码基因的表达。在目前的研究中，我们评估了 RRMS 患者在接受芬戈莫德治疗时外周血中 miR-506-3p、miR-217、miR-381-3p、miR-1827、miR-449a 和 miR-655-3p 的表达情况，并与健康对照组进行了比较。我们还比较了这些 miRNA 在芬戈莫德应答者和无应答者之间的表达情况，以确定它们与芬戈莫德应答的相关性。应答者 miR-381-3p 的表达明显高于对照组（RE 差异=3.903，P=0.005），而应答者和无应答者的 miR-655-3p 表达均明显低于对照组（RE 差异=-1.03，P=0.014；RE 差异=-1.41，P<0.0001）。研究亚组之间其他 miRNA 的表达无差异。此外，应答者和无应答者之间任何 miRNA 的表达均无差异。虽然在对照组中所有评估的 miRNA 的表达水平之间存在显著的两两相关性，但 MS 患者的相关性模式存在差异。应答者 miR-381-3p 的表达与年龄相关。然而，在任何研究亚组中，其他 miRNA 的表达均与年龄无关。本研究表明 miR-655-3p 和 miR-381-3p 可能在 MS 的发病机制中起作用，或者芬戈莫德对这些 miRNA 的表达可能有影响。需要进一步的研究来在更大的患者群体中验证这些结果。
