National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.
National and Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, China.
Mol Cell Biochem. 2023 Dec;478(12):2891-2906. doi: 10.1007/s11010-023-04705-3. Epub 2023 Mar 21.
Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.
胃腺癌（Gastric adenocarcinoma，GAC）是世界上最致命的恶性肿瘤之一。已经证实，GAC 的发生和发展与分子变化有关。然而，GAC 的发病机制仍不清楚。在本研究中，我们对 6 对 GAC 肿瘤组织和相邻正常组织进行了测序，并从 TCGA 数据库中收集了 GAC 基因表达谱数据。对这些数据的分析揭示了 465 个差异表达基因（Differentially expressed genes，DEGs），其中 246 个上调，219 个下调。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路分析表明，DEGs 在细胞外基质-受体相互作用、蛋白质消化吸收和胃酸分泌通路中明显富集。通过生存分析，从蛋白质-蛋白质相互作用（Protein-protein interaction，PPI）网络中筛选出与 GAC 预后不良相关的 6 个关键基因（MATN3、COL1A1、COL5A2、P4HA3、SERPINE1 和 VCAN），其中 P4HA3 和 MATN3 很少被报道与 GAC 有关。我们进一步通过 RT-qPCR、MTT、流式细胞术、集落形成、划痕愈合、Transwell 和 Western blot 实验分析了 P4HA3 在 GAC 细胞系 SGC-7901 中的功能。我们发现 P4HA3 在 SGC-7901 细胞系中上调，而在正常对照细胞中下调。功能丧失实验的结果表明，P4HA3 显著增强了 GAC 细胞的增殖和迁移能力。本研究为 GAC 预后标志物和治疗靶点的选择提供了新的依据。
