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Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a prevalent aortic disease that causes high mortality due to asymptomatic gradual expansion and sudden rupture. The underlying molecular mechanisms and effective pharmaceutical therapy for preventing AAA progression have not been fully identified. In this study, we...

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Autores principales: Kan, Ke-Jia, Guo, Feng, Zhu, Lei, Pallavi, Prama, Sigl, Martin, Keese, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152975/
https://www.ncbi.nlm.nih.gov/pubmed/34068179
http://dx.doi.org/10.3390/biomedicines9050546
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author Kan, Ke-Jia
Guo, Feng
Zhu, Lei
Pallavi, Prama
Sigl, Martin
Keese, Michael
author_facet Kan, Ke-Jia
Guo, Feng
Zhu, Lei
Pallavi, Prama
Sigl, Martin
Keese, Michael
author_sort Kan, Ke-Jia
collection PubMed
description Abdominal aortic aneurysm (AAA) is a prevalent aortic disease that causes high mortality due to asymptomatic gradual expansion and sudden rupture. The underlying molecular mechanisms and effective pharmaceutical therapy for preventing AAA progression have not been fully identified. In this study, we identified the key modules and hub genes involved in AAA growth from the GSE17901 dataset in the Gene Expression Omnibus (GEO) database through the weighted gene co-expression network analysis (WGCNA). Key genes were further selected and validated in the mouse dataset (GSE12591) and human datasets (GSE7084, GSE47472, and GSE57691). Finally, we predicted drug candidates targeting key genes using the Drug–Gene Interaction database. Overall, we identified key modules enriched in the mitotic cell cycle, GTPase activity, and several metabolic processes. Seven key genes (CCR5, ADCY5, ADCY3, ACACB, LPIN1, ACSL1, UCP3) related to AAA progression were identified. A total of 35 drugs/compounds targeting the key genes were predicted, which may have the potential to prevent AAA progression.
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spelling pubmed-81529752021-05-27 Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm Kan, Ke-Jia Guo, Feng Zhu, Lei Pallavi, Prama Sigl, Martin Keese, Michael Biomedicines Article Abdominal aortic aneurysm (AAA) is a prevalent aortic disease that causes high mortality due to asymptomatic gradual expansion and sudden rupture. The underlying molecular mechanisms and effective pharmaceutical therapy for preventing AAA progression have not been fully identified. In this study, we identified the key modules and hub genes involved in AAA growth from the GSE17901 dataset in the Gene Expression Omnibus (GEO) database through the weighted gene co-expression network analysis (WGCNA). Key genes were further selected and validated in the mouse dataset (GSE12591) and human datasets (GSE7084, GSE47472, and GSE57691). Finally, we predicted drug candidates targeting key genes using the Drug–Gene Interaction database. Overall, we identified key modules enriched in the mitotic cell cycle, GTPase activity, and several metabolic processes. Seven key genes (CCR5, ADCY5, ADCY3, ACACB, LPIN1, ACSL1, UCP3) related to AAA progression were identified. A total of 35 drugs/compounds targeting the key genes were predicted, which may have the potential to prevent AAA progression. MDPI 2021-05-13 /pmc/articles/PMC8152975/ /pubmed/34068179 http://dx.doi.org/10.3390/biomedicines9050546 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kan, Ke-Jia
Guo, Feng
Zhu, Lei
Pallavi, Prama
Sigl, Martin
Keese, Michael
Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm
title Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm
title_full Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm
title_fullStr Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm
title_full_unstemmed Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm
title_short Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm
title_sort weighted gene co-expression network analysis reveals key genes and potential drugs in abdominal aortic aneurysm
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152975/
https://www.ncbi.nlm.nih.gov/pubmed/34068179
http://dx.doi.org/10.3390/biomedicines9050546
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