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多发性硬化症患者接受芬戈莫德治疗后 microRNAs 表达谱的评估。

Assessment of expression profile of microRNAs in multiple sclerosis patients treated with fingolimod.

机构信息

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Neurology, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

J Mol Neurosci. 2020 Aug;70(8):1274-1281. doi: 10.1007/s12031-020-01537-4. Epub 2020 Mar 25.

Abstract

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.

摘要

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。

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