Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism

Abstract Venous thromboembolism (VTE) is a complex, multifactorial life-threatening disease that involves vascular endothelial cell (VEC) dysfunction. However, the exact pathogenesis and underlying mechanisms of VTE are not completely clear. The aim of this study was to identify the core genes and p...

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Autores principales:	Yiming Su, Qiyi Li, Zhiyong Zheng, Xiaomin Wei, Peiyong Hou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6342471234cd4f7b9bfedaff754dc2e4
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spelling	oai:doaj.org-article:6342471234cd4f7b9bfedaff754dc2e42021-12-02T19:06:38ZIdentification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism10.1038/s41598-021-95909-42045-2322https://doaj.org/article/6342471234cd4f7b9bfedaff754dc2e42021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95909-4https://doaj.org/toc/2045-2322Abstract Venous thromboembolism (VTE) is a complex, multifactorial life-threatening disease that involves vascular endothelial cell (VEC) dysfunction. However, the exact pathogenesis and underlying mechanisms of VTE are not completely clear. The aim of this study was to identify the core genes and pathways in VECs that are involved in the development and progression of unprovoked VTE (uVTE). The microarray dataset GSE118259 was downloaded from the Gene Expression Omnibus database, and 341 up-regulated and 8 down-regulated genes were identified in the VTE patients relative to the healthy controls, including CREB1, HIF1α, CBL, ILK, ESM1 and the ribosomal protein family genes. The protein–protein interaction (PPI) network and the transcription factor (TF)-miRNA-target gene network were constructed with these differentially expressed genes (DEGs), and visualized using Cytoscape software 3.6.1. Eighty-nine miRNAs were predicted as the targeting miRNAs of the DEGs, and 197 TFs were predicted as regulators of these miRNAs. In addition, 237 node genes and 4 modules were identified in the PPI network. The significantly enriched pathways included metabolic, cell adhesion, cell proliferation and cellular response to growth factor stimulus pathways. CREB1 was a differentially expressed TF in the TF-miRNA-target gene network, which regulated six miRNA-target gene pairs. The up-regulation of ESM1, HIF1α and CREB1 was confirmed at the mRNA and protein level in the plasma of uVTE patients. Taken together, ESM1, HIF1α and the CREB1-miRNA-target genes axis play potential mechanistic roles in uVTE development.Yiming SuQiyi LiZhiyong ZhengXiaomin WeiPeiyong HouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yiming Su Qiyi Li Zhiyong Zheng Xiaomin Wei Peiyong Hou Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism
description	Abstract Venous thromboembolism (VTE) is a complex, multifactorial life-threatening disease that involves vascular endothelial cell (VEC) dysfunction. However, the exact pathogenesis and underlying mechanisms of VTE are not completely clear. The aim of this study was to identify the core genes and pathways in VECs that are involved in the development and progression of unprovoked VTE (uVTE). The microarray dataset GSE118259 was downloaded from the Gene Expression Omnibus database, and 341 up-regulated and 8 down-regulated genes were identified in the VTE patients relative to the healthy controls, including CREB1, HIF1α, CBL, ILK, ESM1 and the ribosomal protein family genes. The protein–protein interaction (PPI) network and the transcription factor (TF)-miRNA-target gene network were constructed with these differentially expressed genes (DEGs), and visualized using Cytoscape software 3.6.1. Eighty-nine miRNAs were predicted as the targeting miRNAs of the DEGs, and 197 TFs were predicted as regulators of these miRNAs. In addition, 237 node genes and 4 modules were identified in the PPI network. The significantly enriched pathways included metabolic, cell adhesion, cell proliferation and cellular response to growth factor stimulus pathways. CREB1 was a differentially expressed TF in the TF-miRNA-target gene network, which regulated six miRNA-target gene pairs. The up-regulation of ESM1, HIF1α and CREB1 was confirmed at the mRNA and protein level in the plasma of uVTE patients. Taken together, ESM1, HIF1α and the CREB1-miRNA-target genes axis play potential mechanistic roles in uVTE development.
format	article
author	Yiming Su Qiyi Li Zhiyong Zheng Xiaomin Wei Peiyong Hou
author_facet	Yiming Su Qiyi Li Zhiyong Zheng Xiaomin Wei Peiyong Hou
author_sort	Yiming Su
title	Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism
title_short	Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism
title_full	Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism
title_fullStr	Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism
title_full_unstemmed	Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism
title_sort	identification of genes, pathways and transcription factor-mirna-target gene networks and experimental verification in venous thromboembolism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6342471234cd4f7b9bfedaff754dc2e4
work_keys_str_mv	AT yimingsu identificationofgenespathwaysandtranscriptionfactormirnatargetgenenetworksandexperimentalverificationinvenousthromboembolism AT qiyili identificationofgenespathwaysandtranscriptionfactormirnatargetgenenetworksandexperimentalverificationinvenousthromboembolism AT zhiyongzheng identificationofgenespathwaysandtranscriptionfactormirnatargetgenenetworksandexperimentalverificationinvenousthromboembolism AT xiaominwei identificationofgenespathwaysandtranscriptionfactormirnatargetgenenetworksandexperimentalverificationinvenousthromboembolism AT peiyonghou identificationofgenespathwaysandtranscriptionfactormirnatargetgenenetworksandexperimentalverificationinvenousthromboembolism
_version_	1718377152849641472

Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism

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