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微小RNA调控的药物-信号通路网络构建揭示了重症肌无力的药物再利用候选药物。

Construction of an miRNA-regulated drug-pathway network reveals drug repurposing candidates for myasthenia gravis.

作者信息

Cao Yuze, Lu Xiaoyan, Wang Jianjian, Zhang Huixue, Liu Zhaojun, Xu Si, Wang Tianfeng, Ning Shangwei, Xiao Bo, Wang Lihua

机构信息

Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

出版信息

Int J Mol Med. 2017 Feb;39(2):268-278. doi: 10.3892/ijmm.2017.2853. Epub 2017 Jan 11.

DOI:10.3892/ijmm.2017.2853
PMID:28075449
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5358695/
Abstract

Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, we created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases. Based on these genes and miRNAs, we identified 41 MG risk pathways and 105 approved drugs that can affect these pathways. Some important MG-related pathways, such as hsa04060 (cytokine-cytokine receptor interaction) and hsa05200 (pathway in cancer), were found to be regulated by MG risk miRNAs and drugs. Furthermore, we constructed an miRNA-regulated drug-pathway network and identified miRNAs and drugs that synergistically regulate key MG pathways and biological processes. We developed a drug repurposing strategy to identify 25 drug repurposing candidates for MG; several of these drugs, such as rituximab, adalimumab, sunitinib, and muromonab, have the potential to be novel MG treatment drugs. This study provides novel insight into the pathogenesis of MG and potential drug candidates for MG were identified.

摘要

重症肌无力(MG)是一种罕见的使人衰弱的自身免疫性神经肌肉疾病。许多研究都聚焦于重症肌无力的发病机制和治疗策略。然而,重症肌无力的确切发病机制和有效的治疗策略仍不明确。最近的研究表明,微小RNA(miRNA或miR)可以调节重症肌无力的病理途径,提示它们在新治疗方法中的潜在作用。在本研究中,我们通过人工挖掘已发表的文献和公共数据库,创建了一个经实验证实的重症肌无力风险基因和miRNA的综合目录。基于这些基因和miRNA,我们确定了41条重症肌无力风险途径以及105种可影响这些途径的获批药物。发现一些重要的重症肌无力相关途径,如hsa04060(细胞因子 - 细胞因子受体相互作用)和hsa05200(癌症中的途径),受重症肌无力风险miRNA和药物的调控。此外,我们构建了一个miRNA调控的药物 - 途径网络,并确定了协同调节重症肌无力关键途径和生物学过程的miRNA和药物。我们开发了一种药物重新利用策略,以确定25种重症肌无力的药物重新利用候选药物;其中几种药物,如利妥昔单抗、阿达木单抗、舒尼替尼和莫罗单抗,有可能成为新型重症肌无力治疗药物。本研究为重症肌无力的发病机制提供了新的见解,并确定了重症肌无力的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2483/5358695/8e5359d1c58f/IJMM-39-02-0268-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2483/5358695/b6df80510200/IJMM-39-02-0268-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2483/5358695/8e5359d1c58f/IJMM-39-02-0268-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2483/5358695/b6df80510200/IJMM-39-02-0268-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2483/5358695/8e5359d1c58f/IJMM-39-02-0268-g08.jpg

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