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P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis

Gastric cancer (GC) is a common tumor-associated lethal disease, and invasiveness and metastasis are primary challenges in its clinical treatment. Hypoxia microenvironment cannot be ignored in the process of metastasis. Hypoxia inducible factor-1α (HIF-1α) is the core component of the hypoxia signal...

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Autores principales: Zhang, Jun, Guo, Shuai, Wu, Yue, Zheng, Zhi-chao, Wang, Yue, Zhao, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699373/
https://www.ncbi.nlm.nih.gov/pubmed/31467922
http://dx.doi.org/10.1155/2019/9749751
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author Zhang, Jun
Guo, Shuai
Wu, Yue
Zheng, Zhi-chao
Wang, Yue
Zhao, Yan
author_facet Zhang, Jun
Guo, Shuai
Wu, Yue
Zheng, Zhi-chao
Wang, Yue
Zhao, Yan
author_sort Zhang, Jun
collection PubMed
description Gastric cancer (GC) is a common tumor-associated lethal disease, and invasiveness and metastasis are primary challenges in its clinical treatment. Hypoxia microenvironment cannot be ignored in the process of metastasis. Hypoxia inducible factor-1α (HIF-1α) is the core component of the hypoxia signaling pathway. The aim of this study was to identify potential hub genes and signaling pathways associated with HIF-1α. We explored the invasiveness- and metastasis-associated phenotype of GC via bioinformatics analysis and molecular studies. Differentially expressed genes (DEGs) were identified in GC cells and HIF-1α-knockdown GC cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified via centrality analysis and Molecular Complex Detection (MCODE) module analysis. The findings suggested that prolyl 4-hydroxylase beta polypeptide (P4HB) has strong associations with HIF-1α. Further, we observed that HIF-1α and P4HB were upregulated in SGC-7901 and BGC-823 cells. In addition, inhibition of HIF-1α expression reduced invasion and metastasis in GC cells; this effect was partially reversed by P4HB overexpression. Our results confirm that P4HB plays a significant role in the regulatory network of HIF-1α. Therefore, HIF-1α and P4HB may be considered potential biomarkers of GC.
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spelling pubmed-66993732019-08-29 P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis Zhang, Jun Guo, Shuai Wu, Yue Zheng, Zhi-chao Wang, Yue Zhao, Yan Biomed Res Int Research Article Gastric cancer (GC) is a common tumor-associated lethal disease, and invasiveness and metastasis are primary challenges in its clinical treatment. Hypoxia microenvironment cannot be ignored in the process of metastasis. Hypoxia inducible factor-1α (HIF-1α) is the core component of the hypoxia signaling pathway. The aim of this study was to identify potential hub genes and signaling pathways associated with HIF-1α. We explored the invasiveness- and metastasis-associated phenotype of GC via bioinformatics analysis and molecular studies. Differentially expressed genes (DEGs) were identified in GC cells and HIF-1α-knockdown GC cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified via centrality analysis and Molecular Complex Detection (MCODE) module analysis. The findings suggested that prolyl 4-hydroxylase beta polypeptide (P4HB) has strong associations with HIF-1α. Further, we observed that HIF-1α and P4HB were upregulated in SGC-7901 and BGC-823 cells. In addition, inhibition of HIF-1α expression reduced invasion and metastasis in GC cells; this effect was partially reversed by P4HB overexpression. Our results confirm that P4HB plays a significant role in the regulatory network of HIF-1α. Therefore, HIF-1α and P4HB may be considered potential biomarkers of GC. Hindawi 2019-07-30 /pmc/articles/PMC6699373/ /pubmed/31467922 http://dx.doi.org/10.1155/2019/9749751 Text en Copyright © 2019 Jun Zhang et al. https://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
Zhang, Jun
Guo, Shuai
Wu, Yue
Zheng, Zhi-chao
Wang, Yue
Zhao, Yan
P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis
title P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis
title_full P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis
title_fullStr P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis
title_full_unstemmed P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis
title_short P4HB, a Novel Hypoxia Target Gene Related to Gastric Cancer Invasion and Metastasis
title_sort p4hb, a novel hypoxia target gene related to gastric cancer invasion and metastasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699373/
https://www.ncbi.nlm.nih.gov/pubmed/31467922
http://dx.doi.org/10.1155/2019/9749751
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