Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis

Abstract Myasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene n...

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Autores principales:	Chunrui Bo, Huixue Zhang, Yuze Cao, Xiaoyu Lu, Cong Zhang, Shuang Li, Xiaotong Kong, Xiaoming Zhang, Ming Bai, Kuo Tian, Aigul Saitgareeva, Gaysina Lyaysan, Jianjian Wang, Shangwei Ning, Lihua Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/218c7dcd85c645919e67f54e28198527
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spelling	oai:doaj.org-article:218c7dcd85c645919e67f54e281985272021-12-02T13:57:48ZConstruction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis10.1038/s41598-021-81962-62045-2322https://doaj.org/article/218c7dcd85c645919e67f54e281985272021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81962-6https://doaj.org/toc/2045-2322Abstract Myasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene network (TMGN) of MG was constructed by extracting six regulatory pairs (TF–miRNA, miRNA–gene, TF–gene, miRNA–TF, gene–gene and miRNA–miRNA). Then, 3/4/5-node regulatory motifs were detected in the TMGN. Then, the motifs with the highest Z-score, occurring as 3/4/5-node composite feed-forward loops (FFLs), were selected as statistically significant motifs. By merging these motifs together, we constructed a 3/4/5-node composite FFL motif-specific subnetwork (CFMSN). Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MG. In addition, the genes, TFs and miRNAs in the CFMSN were also utilized to identify potential drugs. Five related genes, 3 TFs and 13 miRNAs, were extracted from the CFMSN. As the most important TF in the CFMSN, MYC was inferred to play a critical role in MG. Pathway enrichment analysis showed that the genes and miRNAs in the CFMSN were mainly enriched in pathways related to cancer and infections. Furthermore, 21 drugs were identified through the CFMSN, of which estradiol, estramustine, raloxifene and tamoxifen have the potential to be novel drugs to treat MG. The present study provides MG-related TFs by constructing the CFMSN for further experimental studies and provides a novel perspective for new biomarkers and potential drugs for MG.Chunrui BoHuixue ZhangYuze CaoXiaoyu LuCong ZhangShuang LiXiaotong KongXiaoming ZhangMing BaiKuo TianAigul SaitgareevaGaysina LyaysanJianjian WangShangwei NingLihua WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunrui Bo Huixue Zhang Yuze Cao Xiaoyu Lu Cong Zhang Shuang Li Xiaotong Kong Xiaoming Zhang Ming Bai Kuo Tian Aigul Saitgareeva Gaysina Lyaysan Jianjian Wang Shangwei Ning Lihua Wang Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
description	Abstract Myasthenia gravis (MG) is an autoimmune disease and the most common type of neuromuscular disease. Genes and miRNAs associated with MG have been widely studied; however, the molecular mechanisms of transcription factors (TFs) and the relationship among them remain unclear. A TF–miRNA–gene network (TMGN) of MG was constructed by extracting six regulatory pairs (TF–miRNA, miRNA–gene, TF–gene, miRNA–TF, gene–gene and miRNA–miRNA). Then, 3/4/5-node regulatory motifs were detected in the TMGN. Then, the motifs with the highest Z-score, occurring as 3/4/5-node composite feed-forward loops (FFLs), were selected as statistically significant motifs. By merging these motifs together, we constructed a 3/4/5-node composite FFL motif-specific subnetwork (CFMSN). Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MG. In addition, the genes, TFs and miRNAs in the CFMSN were also utilized to identify potential drugs. Five related genes, 3 TFs and 13 miRNAs, were extracted from the CFMSN. As the most important TF in the CFMSN, MYC was inferred to play a critical role in MG. Pathway enrichment analysis showed that the genes and miRNAs in the CFMSN were mainly enriched in pathways related to cancer and infections. Furthermore, 21 drugs were identified through the CFMSN, of which estradiol, estramustine, raloxifene and tamoxifen have the potential to be novel drugs to treat MG. The present study provides MG-related TFs by constructing the CFMSN for further experimental studies and provides a novel perspective for new biomarkers and potential drugs for MG.
format	article
author	Chunrui Bo Huixue Zhang Yuze Cao Xiaoyu Lu Cong Zhang Shuang Li Xiaotong Kong Xiaoming Zhang Ming Bai Kuo Tian Aigul Saitgareeva Gaysina Lyaysan Jianjian Wang Shangwei Ning Lihua Wang
author_facet	Chunrui Bo Huixue Zhang Yuze Cao Xiaoyu Lu Cong Zhang Shuang Li Xiaotong Kong Xiaoming Zhang Ming Bai Kuo Tian Aigul Saitgareeva Gaysina Lyaysan Jianjian Wang Shangwei Ning Lihua Wang
author_sort	Chunrui Bo
title	Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
title_short	Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
title_full	Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
title_fullStr	Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
title_full_unstemmed	Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
title_sort	construction of a tf–mirna–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/218c7dcd85c645919e67f54e28198527
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Construction of a TF–miRNA–gene feed-forward loop network predicts biomarkers and potential drugs for myasthenia gravis

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