Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse

Abstract Background Chronic chagasic cardiomyopathy (CCC) is the leading cause of heart failure in Latin America and often causes severe inflammation and fibrosis in the heart. Studies on myocardial function and its molecular mechanisms in patients with Chronic chagasic cardiomyopathy are very limit...

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Autores principales:	Jiahe Wu, Jianlei Cao, Yongzhen Fan, Chenze Li, Xiaorong Hu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Chronic chagasic cardiomyopathy Hub gene miRNA–mRNA regulatory network Gene function enrichment analysis PPI network Bioinformatics analysis Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fa9f1df56de54bd19ad70e7f5f1c1dc4
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spelling	oai:doaj.org-article:fa9f1df56de54bd19ad70e7f5f1c1dc42021-12-05T12:05:26ZComprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse10.1186/s12920-021-01134-31755-8794https://doaj.org/article/fa9f1df56de54bd19ad70e7f5f1c1dc42021-11-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01134-3https://doaj.org/toc/1755-8794Abstract Background Chronic chagasic cardiomyopathy (CCC) is the leading cause of heart failure in Latin America and often causes severe inflammation and fibrosis in the heart. Studies on myocardial function and its molecular mechanisms in patients with Chronic chagasic cardiomyopathy are very limited. In order to understand the development and progression of Chronic chagasic cardiomyopathy and find targets for its diagnosis and treatment, the field needs to better understand the exact molecular mechanisms involved in these processes. Methods The mRNA microarray datasets GSE84796 (human) and GSE24088 (mouse) were obtained from the Gene Expression Omnibus (GEO) database. Homologous genes between the two species were identified using the online database mining tool Biomart, followed by differential expression analysis, gene enrichment analysis and protein–protein interaction (PPI) network construction. Cytohubba plug-in of Cytoscape software was used to identify Hub gene, and miRNet was used to construct the corresponding miRNA–mRNA regulatory network. miRNA-related databases: miRDB, Targetscan and miRWalk were used to further evaluate miRNAs in the miRNA–mRNA network. Furthermore, Comparative Toxicogenomics Database (CTD) and L1000 Platform were used to identify hub gene-related drugs. Results A total of 86 homologous genes were significantly differentially expressed in the two datasets, including 73 genes with high expression and 13 genes with low expression. These differentially expressed genes were mainly enriched in the terms of innate immune response, signal transduction, protein binding, Natural killer cell mediated cytotoxicity, Tuberculosis, Chemokine signaling pathway, Chagas disease and PI3K−Akt signaling pathway. The top 10 hub genes LAPTM5, LCP1, HCLS1, CORO1A, CD48, TYROBP, RAC2, ARHGDIB, FERMT3 and NCF4 were identified from the PPI network. A total of 122 miRNAs were identified to target these hub genes and 30 of them regulated two or more hub genes at the same time. miRDB, Targetscan and miRWalk were further analyzed and screened out hsa-miR-34c-5p, hsa-miR-34a-5p and hsa-miR-16-5p as miRNAs regulating these hub genes. Finally, Progesterone, Flutamide, Nimesulide, Methotrexate and Temozolomide were identified to target these hub genes and might be targeted therapies for Chronic chagasic cardiomyopathy. Conclusions In this study, the potential genes associated with Chronic chagasic cardiomyopathy are identified and a miRNA–mRNA regulatory network is constructed. This study explores the molecular mechanisms of Chronic chagasic cardiomyopathy and provides important clues for finding new therapeutic targets.Jiahe WuJianlei CaoYongzhen FanChenze LiXiaorong HuBMCarticleChronic chagasic cardiomyopathyHub genemiRNA–mRNA regulatory networkGene function enrichment analysisPPI networkBioinformatics analysisInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chronic chagasic cardiomyopathy Hub gene miRNA–mRNA regulatory network Gene function enrichment analysis PPI network Bioinformatics analysis Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	Chronic chagasic cardiomyopathy Hub gene miRNA–mRNA regulatory network Gene function enrichment analysis PPI network Bioinformatics analysis Internal medicine RC31-1245 Genetics QH426-470 Jiahe Wu Jianlei Cao Yongzhen Fan Chenze Li Xiaorong Hu Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
description	Abstract Background Chronic chagasic cardiomyopathy (CCC) is the leading cause of heart failure in Latin America and often causes severe inflammation and fibrosis in the heart. Studies on myocardial function and its molecular mechanisms in patients with Chronic chagasic cardiomyopathy are very limited. In order to understand the development and progression of Chronic chagasic cardiomyopathy and find targets for its diagnosis and treatment, the field needs to better understand the exact molecular mechanisms involved in these processes. Methods The mRNA microarray datasets GSE84796 (human) and GSE24088 (mouse) were obtained from the Gene Expression Omnibus (GEO) database. Homologous genes between the two species were identified using the online database mining tool Biomart, followed by differential expression analysis, gene enrichment analysis and protein–protein interaction (PPI) network construction. Cytohubba plug-in of Cytoscape software was used to identify Hub gene, and miRNet was used to construct the corresponding miRNA–mRNA regulatory network. miRNA-related databases: miRDB, Targetscan and miRWalk were used to further evaluate miRNAs in the miRNA–mRNA network. Furthermore, Comparative Toxicogenomics Database (CTD) and L1000 Platform were used to identify hub gene-related drugs. Results A total of 86 homologous genes were significantly differentially expressed in the two datasets, including 73 genes with high expression and 13 genes with low expression. These differentially expressed genes were mainly enriched in the terms of innate immune response, signal transduction, protein binding, Natural killer cell mediated cytotoxicity, Tuberculosis, Chemokine signaling pathway, Chagas disease and PI3K−Akt signaling pathway. The top 10 hub genes LAPTM5, LCP1, HCLS1, CORO1A, CD48, TYROBP, RAC2, ARHGDIB, FERMT3 and NCF4 were identified from the PPI network. A total of 122 miRNAs were identified to target these hub genes and 30 of them regulated two or more hub genes at the same time. miRDB, Targetscan and miRWalk were further analyzed and screened out hsa-miR-34c-5p, hsa-miR-34a-5p and hsa-miR-16-5p as miRNAs regulating these hub genes. Finally, Progesterone, Flutamide, Nimesulide, Methotrexate and Temozolomide were identified to target these hub genes and might be targeted therapies for Chronic chagasic cardiomyopathy. Conclusions In this study, the potential genes associated with Chronic chagasic cardiomyopathy are identified and a miRNA–mRNA regulatory network is constructed. This study explores the molecular mechanisms of Chronic chagasic cardiomyopathy and provides important clues for finding new therapeutic targets.
format	article
author	Jiahe Wu Jianlei Cao Yongzhen Fan Chenze Li Xiaorong Hu
author_facet	Jiahe Wu Jianlei Cao Yongzhen Fan Chenze Li Xiaorong Hu
author_sort	Jiahe Wu
title	Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
title_short	Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
title_full	Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
title_fullStr	Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
title_full_unstemmed	Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
title_sort	comprehensive analysis of mirna–mrna regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse
publisher	BMC
publishDate	2021
url	https://doaj.org/article/fa9f1df56de54bd19ad70e7f5f1c1dc4
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Comprehensive analysis of miRNA–mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse

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