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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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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. |
format | Online Article Text |
id | pubmed-6699373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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