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

• Published in: BioMed research international 2019, Vol.2019 (2019), p.1-13
• Main Authors: Wang, Yue, Zheng, Zhi-chao, Wu, Yue, Guo, Shuai, Zhang, Jun, Zhao, Yan
• Format: Article
• Language: English
• Subjects: Biochemistry; Bioinformatics; Biomarkers; Cancer; Cancer therapies; Carcinogenesis - genetics; Cell growth; Cell Line, Tumor; Cell Proliferation - genetics; Computational Biology; Encyclopedias; Endoplasmic reticulum; Gastric cancer; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Genes; Genetic aspects; Genomes; Genomics; Humans; Hydroxylase; Hydroxylases; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Invasiveness; Medical prognosis; Medical research; Metastases; Metastasis; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Neoplasm Metastasis; Oncology; Ontology; Ovarian cancer; Phenotypes; Procollagen-proline dioxygenase; Procollagen-Proline Dioxygenase - genetics; Protein Disulfide-Isomerases - genetics; Protein interaction; Protein Interaction Maps - genetics; Protein-protein interactions; Proteins; Signal transduction; Signal Transduction - genetics; Signaling; Software; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Studies; Tumor Hypoxia - genetics; Tumor Microenvironment - genetics
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2019/9749751

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.