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Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury

Liver ischemia/reperfusion (I/R) injury is a complex and common clinical disease with limited therapeutic options. The aim of our study was to discover the candidate target genes in liver I/R injury and to further elucidate the potential regulatory mechanisms, especially the ones involving transcrip...

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Autores principales: Zhong, Yiming, Zhu, Youwei, Dong, Junfeng, Zhou, Wei, Xiong, Cheng, Xue, Meilin, Shi, Minmin, Chen, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875376/
https://www.ncbi.nlm.nih.gov/pubmed/31781649
http://dx.doi.org/10.1155/2019/8962682
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author Zhong, Yiming
Zhu, Youwei
Dong, Junfeng
Zhou, Wei
Xiong, Cheng
Xue, Meilin
Shi, Minmin
Chen, Hao
author_facet Zhong, Yiming
Zhu, Youwei
Dong, Junfeng
Zhou, Wei
Xiong, Cheng
Xue, Meilin
Shi, Minmin
Chen, Hao
author_sort Zhong, Yiming
collection PubMed
description Liver ischemia/reperfusion (I/R) injury is a complex and common clinical disease with limited therapeutic options. The aim of our study was to discover the candidate target genes in liver I/R injury and to further elucidate the potential regulatory mechanisms, especially the ones involving transcription factors and miRNAs. The analysis of mouse data set GSE10657 from Gene Expression Omnibus database (GEO) revealed 203 differentially expressed genes (DEGs) including 19 transcription factors (TFs). Functional and pathway enrichment analyses were conducted to explore their biological functions. We further obtained the targets of TFs and miRNAs, to form our TF-mRNA/TF-miRNA-mRNA co-regulatory network. In our network, we found that the important subunits of activator protein 1 (AP-1) including JUN, FOS and ATF3, were hub genes in liver I/R injury. AP-1 target genes were activated in our mouse models. AP-1 could transcriptionally activate phosphatase and tensin homolog (PTEN) while AP-1-dependent miRNAs countered this effect. In conclusion, this study suggested that AP-1, together with AP-1-dependent miRNAs formed a co-regulatory network enabling AP-1 target genes to be tightly controlled, which will complete the mechanism of liver ischemia/reperfusion injury and provide direction for finding potential therapeutic targets.
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spelling pubmed-68753762019-11-28 Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury Zhong, Yiming Zhu, Youwei Dong, Junfeng Zhou, Wei Xiong, Cheng Xue, Meilin Shi, Minmin Chen, Hao Biomed Res Int Research Article Liver ischemia/reperfusion (I/R) injury is a complex and common clinical disease with limited therapeutic options. The aim of our study was to discover the candidate target genes in liver I/R injury and to further elucidate the potential regulatory mechanisms, especially the ones involving transcription factors and miRNAs. The analysis of mouse data set GSE10657 from Gene Expression Omnibus database (GEO) revealed 203 differentially expressed genes (DEGs) including 19 transcription factors (TFs). Functional and pathway enrichment analyses were conducted to explore their biological functions. We further obtained the targets of TFs and miRNAs, to form our TF-mRNA/TF-miRNA-mRNA co-regulatory network. In our network, we found that the important subunits of activator protein 1 (AP-1) including JUN, FOS and ATF3, were hub genes in liver I/R injury. AP-1 target genes were activated in our mouse models. AP-1 could transcriptionally activate phosphatase and tensin homolog (PTEN) while AP-1-dependent miRNAs countered this effect. In conclusion, this study suggested that AP-1, together with AP-1-dependent miRNAs formed a co-regulatory network enabling AP-1 target genes to be tightly controlled, which will complete the mechanism of liver ischemia/reperfusion injury and provide direction for finding potential therapeutic targets. Hindawi 2019-11-05 /pmc/articles/PMC6875376/ /pubmed/31781649 http://dx.doi.org/10.1155/2019/8962682 Text en Copyright © 2019 Yiming Zhong et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhong, Yiming
Zhu, Youwei
Dong, Junfeng
Zhou, Wei
Xiong, Cheng
Xue, Meilin
Shi, Minmin
Chen, Hao
Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury
title Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury
title_full Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury
title_fullStr Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury
title_full_unstemmed Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury
title_short Identification of Key Transcription Factors AP-1 and AP-1-Dependent miRNAs Forming a Co-Regulatory Network Controlling PTEN in Liver Ischemia/Reperfusion Injury
title_sort identification of key transcription factors ap-1 and ap-1-dependent mirnas forming a co-regulatory network controlling pten in liver ischemia/reperfusion injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875376/
https://www.ncbi.nlm.nih.gov/pubmed/31781649
http://dx.doi.org/10.1155/2019/8962682
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