Gastric Cancer Department, Liaoning Province Cancer Hospital & Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, China.
Emergency Department, Shengjing Hospital of China Medical University, 36 Sanhao St., Heping District, Shenyang, Liaoning, 110003, China.
Biomed Res Int. 2019 Jul 30;2019:9749751. doi: 10.1155/2019/9749751. eCollection 2019.
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-1 (HIF-1) 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-1. 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-1-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 () has strong associations with HIF-1. Further, we observed that HIF-1 and were upregulated in SGC-7901 and BGC-823 cells. In addition, inhibition of HIF-1 expression reduced invasion and metastasis in GC cells; this effect was partially reversed by overexpression. Our results confirm that plays a significant role in the regulatory network of HIF-1. Therefore, HIF-1 and may be considered potential biomarkers of GC.
胃癌（GC）是一种常见的与肿瘤相关的致命疾病，侵袭性和转移性是其临床治疗的主要挑战。在转移过程中，缺氧微环境不容忽视。缺氧诱导因子-1（HIF-1）是缺氧信号通路的核心组成部分。本研究旨在确定与 HIF-1 相关的潜在枢纽基因和信号通路。我们通过生物信息学分析和分子研究探讨了 GC 的侵袭性和转移性相关表型。鉴定了 GC 细胞和 HIF-1 敲低 GC 细胞中的差异表达基因（DEGs）。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，并构建了蛋白质-蛋白质相互作用（PPI）网络。通过中心性分析和分子复合物检测（MCODE）模块分析鉴定了枢纽基因。研究结果表明，脯氨酰 4-羟化酶 β 多肽（）与 HIF-1 有很强的关联。此外，我们观察到 SGC-7901 和 BGC-823 细胞中 HIF-1 和 上调。此外，抑制 HIF-1 表达可降低 GC 细胞的侵袭和转移；而过表达 可部分逆转这种作用。我们的研究结果证实，在 HIF-1 的调控网络中，发挥着重要作用。因此，HIF-1 和 可能被认为是 GC 的潜在生物标志物。
