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

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

doi:10.3892/ijmm.2017.2853

Cited by 13 publications

(20 citation statements)

References 60 publications

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“…Moreover, exosomal miR-106a-5p expression was shown to be negatively correlated with patient QMGS, indicating its association with MG clinical typing and severity. Interestingly, one of the dysregulated miRNAs by deep-sequencing in the present study, miR-106a-5p has been previously shown to be associated with the pathogenesis of many cancers, including melanoma, colorectal and gastric cancer, MG, [24][25][26] and esophageal squamous-cell carcinoma. [27][28][29][30] Similarly, miR-106a-5p dysregulation has been reported in T-cells of patients with immune diseases, and may inhibit the proliferation, migration, and invasion of carcinoma cells by modulating various mRNA targets.…”

Section: Discussionmentioning

confidence: 63%

Plasma exosomal miR‐106a‐5p expression in myasthenia gravis

Bao

Liang

et al. 2020

Muscle and Nerve

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Background Exosomal miRNA expression for myasthenia gravis (MG) has not been studied. Methods Plasma samples from 92 patients with MG and 49 age‐matched healthy controls (HCs) were screened (by means of deep sequencing and quantitative real‐time polymerase chain reaction) for differentially expressed exosomal microRNA (miRNAs). miR‐106a‐5p was chosen to further verify because it is reportedly involved in MG pathogenesis. Spearman's correlation analysis was used to assess correlations between candidate miRNAs and patient quantitative MG scores (QMGSs). Area under the curve (AUC) of the receiver operating characteristic analysis was used to evaluate the diagnostic accuracy of the identified miRNAs for MG. Results miR‐106a‐5p levels were significantly decreased in MG patients compared with HCs, and were associated with patient QMGS. The AUC values for hsa‐miR‐106a‐5p were 0.728 and 0.813 in ocular and generalized MG patients, respectively. Conclusions Exosomal miR‐106a‐5p was expressed differently in different types of MG and was associated with MG severity.

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Section: Discussionmentioning

confidence: 63%

Plasma exosomal miR‐106a‐5p expression in myasthenia gravis

Bao

Liang

et al. 2020

Muscle and Nerve

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“…Human MG risk gene data was acquired using the following two approaches: i) Gene information was obtained by searching certain current databases, including DisGeNET (http://www.disgenet. org/web/DisGeNET/menu) (15) and Online Mendelian Inheritance in Man (http://www.omim.org/) (16); and ii) using the protocols published in our previous studies (6,7), the gene was notably differentially expressed in more than five MG samples using dependable biological laboratorial techniques, and 9,514 items were browsed by manually collecting literature using the terms [myasthenia gravis (MeSH Terms) and English (Language)] and the species 'Homo sapiens' published prior to March 1st, 2017 on the PubMed database (https://www.ncbi. nlm.nih.gov/pubmed); the eligible genes were selected.…”

Section: Methodsmentioning

confidence: 99%

“…nlm.nih.gov/pubmed); the eligible genes were selected. An update was made to the previous catalog of 162 MG risk genes described in our previous study (7) to 245.…”

Section: Methodsmentioning

confidence: 99%

“…However, the majority of previous studies investigating MG risk genes have focused on only one or a few genes in cell lines without global analysis. Searches for a number of MG risk genes were performed in our previous studies (6,7), however, the risk genes identified previously were not sufficiently comprehensive. The global pathway analysis of MG risk genes in the present study may assist in further characterizing the pathogenesis of MG.…”

Section: Introductionmentioning

confidence: 99%

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Global pathway view analysis of microRNA clusters in myasthenia gravis

Wang

Zhang

et al. 2019

Mol Med Report

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The significant roles of microRNAs (miRNAs) in the pathogenesis of myasthenia gravis (MG) have been observed in numerous previous studies. The impact of miRNA clusters on immunity has been demonstrated in previous years; however, the regulation of miRNA clusters in MG remains to be elucidated. In the present study, 245 MG risk genes were collected and 99 MG risk pathways enriched by these genes were identified. A catalog of 126 MG risk miRNAs was then created; the MG risk miRNAs were located on each chromosome and a miRNA cluster was defined as a number of miRNAs with a relative distance of <6 kb on the same sub-band, same band, same region and same chromosome. Furthermore, enrichment analyses were performed using the target genes of the MG risk miRNA clusters, and a number of risk pathways of each miRNA clusters were identified. As a result, 15 significant miRNA clusters associated with MG were identified. Additionally, the most significant pathways of the miRNA clusters were identified to be enriched on chromosomes 9, 19 and 22, characterized by immunity, infection and carcinoma, suggesting that the mechanism of MG may be associated with certain abnormalities of miRNA clusters on chromosomes 9, 19 and 22. The present study provides novel insight into a global pathway view of miRNA clusters in the pathogenesis of MG.

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“…Regarding the treatment options, immune suppression, thymectomy, intravenous immunoglobulin and plasma exchange are the widely used methods, and prednisolone and azathioprine are commonly administered drugs [9]. The involvement of microRNAs (miRs) in the regulation of the pathological pathways of MG has been previously studied, highlighting their potential role as novel therapeutic pathways [10]. …”

Section: Introductionmentioning

confidence: 99%

MicroRNA-653 Inhibits Thymocyte Proliferation and Induces Thymocyte Apoptosis in Mice with Autoimmune Myasthenia Gravis by Downregulating TRIM9

Cao

Dong²,

et al. 2019

Neuroimmunomodulation

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Objectives: Myasthenia gravis (MG) is an organ-specific autoimmune neuromuscular disorder that occurs as a result of the impairment in neuromuscular junction and autoantibody attack on the postsynaptic receptors. Increasing evidence suggests that microRNAs (miRs) might be involved in the development of MG. Therefore, the present study aimed to investigate the regulatory function of miR-653 on MG and its relationship with tripartite motif 9 (TRIM9). Methods: The thymic tissues obtained from MG patients with thymic hyperplasia were prepared for establishing an MG mouse model in BALB/c mice. Afterwards, the miR-653 and TRIM9 expressions were determined in thymic tissues. A dual-luciferase reporter assay was carried out to validate whether miR-653 directly targets TRIM9. Finally, the thymocytes were exposed to mimics or inhibitors of miR-653, or siRNA against TRIM9 with the use of MTT assays and flow cytometry for the verification of the gain or loss function of miR-653 and TRIM9 on viability, cell cycle progression, and apoptosis of thymocytes. Results: There was a decrease in thymocyte miR-653 and an increase in TRIM9 in thymic tissues of MG mice. miR-653 was found to negatively regulate TRIM9. Overexpression of miR-653 or depletion of TRIM9 resulted in the inhibition of cell viability, suppression of cell cycle progression, and induction of apoptosis rate in thymocytes. Conclusion: The findings from the present study provided evidence that miR-653 impairs proliferation and promotes apoptosis of thymocytes of MG mice by suppressing TRIM9, indicating that miR-653 could be used as potential therapeutic target in the treatment of autoimmune MG.

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

Cited by 13 publications

References 60 publications

Plasma exosomal miR‐106a‐5p expression in myasthenia gravis

Plasma exosomal miR‐106a‐5p expression in myasthenia gravis

Global pathway view analysis of microRNA clusters in myasthenia gravis

MicroRNA-653 Inhibits Thymocyte Proliferation and Induces Thymocyte Apoptosis in Mice with Autoimmune Myasthenia Gravis by Downregulating TRIM9

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