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整合 miRNA 数据集分析:复发性缓解型多发性硬化症患者中 EBV 与维生素 D 之间可能缺失的连接子。

Integrational analysis of miRNAs data sets as a plausible missing linker between Epstein-Barr virus and vitamin D in relapsing remitting MS patients.

机构信息

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.

出版信息

Gene. 2019 Mar 20;689:1-10. doi: 10.1016/j.gene.2018.12.004. Epub 2018 Dec 12.

Abstract

Given the multifactorial state of autoimmune complex diseases such as multiple sclerosis (MS), it is not clear if different risk factors act jointly or independently. Despite intensive studies investigating multi aspects of MS risk factors, findings with regards to potential biomarkers that may link these risk factors remained largely inconclusive. System biology or data integration utilizes different validated datasets to extract meaningful information and map the plausible biological pathways and networks. As such, we integrated eight transcriptome datasets to find the differentially expressed miRNAs in peripheral blood (PB) between relapsing remitting MS patients (RRMS) and normal group. After identification the targeted genes of miRNAs, the hub genes were used to construct the underlying protein-protein interaction network and signaling pathways. As results, 9 miRNAs were best exemplified by significant dysregulation including hsa-mir-15a, hsa-mir-484, hsa-mir-30d, hsa-mir-145, hsa-mir-363, has-let-7e, hsa-mir-30a, hsa-let-7b, and hsa-mir-146a. System biology analysis of miRNAs in PB of RRMS patients clearly indicates the involvement of miRNAs in many vital pathways and highlighted the possibility of an association between miRNAs with EBV and vitamin D in MS pathogenesis. Described novel pathways and genes related to miRNAs such as Transient receptor potential channels and Acid sphingomyelinase may provide a potential target for therapeutic approaches although further functional studies are warranted to test these candidates.

摘要

鉴于多发性硬化症(MS)等自身免疫复合物疾病的多因素状态,不同的风险因素是否共同或独立起作用尚不清楚。尽管对 MS 风险因素的多方面进行了深入研究,但关于可能将这些风险因素联系起来的潜在生物标志物的发现仍然没有定论。系统生物学或数据集成利用不同的经过验证的数据集来提取有意义的信息,并绘制可能的生物学途径和网络。因此,我们整合了八个转录组数据集,以发现在复发缓解型 MS 患者(RRMS)和正常组之间外周血(PB)中差异表达的 miRNA。鉴定 miRNA 的靶向基因后,使用枢纽基因构建潜在的蛋白质-蛋白质相互作用网络和信号通路。结果,9 个 miRNA 的表达显著失调,包括 hsa-mir-15a、hsa-mir-484、hsa-mir-30d、hsa-mir-145、hsa-mir-363、has-let-7e、hsa-mir-30a、hsa-let-7b 和 hsa-mir-146a。RRMS 患者 PB 中 miRNA 的系统生物学分析清楚地表明,miRNA 参与了许多重要途径,并强调了 miRNA 与 EBV 和维生素 D 之间在 MS 发病机制中的关联的可能性。描述的与 miRNA 相关的新途径和基因,如瞬时受体电位通道和酸性鞘磷脂酶,可能为治疗方法提供潜在的靶点,尽管需要进一步的功能研究来测试这些候选物。

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