Department of Oncology, Nantong Haimen People's Hospital, Nantong, 226199, China.
Department of Thoracic Surgery, Nantong University Affiliated Hospital, Nantong, 226001, China.
Sci Rep. 2024 Nov 16;14(1):28355. doi: 10.1038/s41598-024-80027-8.
Gastric cancer (GC) is a leading cause of cancer-related mortality, with a high rate of postoperative recurrence and poor long-term survival. The Eyes Absent (EYA) protein family plays a significant role in cancer progression, with EYA3 being implicated in promoting GC cell proliferation and tumor growth. Utilizing the DepMap database, we identified EYA3 as a gene of interest in GC. We analyzed EYA3 expression in GC tissues and cell lines, performed in vitro assays to assess its role in cell proliferation, and conducted gene set enrichment analysis to explore its relationship with autophagy and the mTORC1 signaling pathway. In vivo, we used a xenograft tumor model to examine the effects of EYA3 expression on tumor progression. EYA3 was consistently upregulated in GC tissues, and its high expression correlated with a decrease in patient survival rates. Silencing EYA3 in GC cell lines resulted in reduced cell proliferation. Inhibition of autophagy and activation of the mTORC1 signaling pathway were observed as mechanisms by which EYA3 may promote GC cell growth. In vivo experiments supported the in vitro findings, showing slower tumor growth with reduced EYA3 expression. Our study confirms the upregulation of EYA3 in GC and its association with poor prognosis. EYA3 promotes GC cell proliferation and tumor growth by activating the mTORC1 signaling pathway and inhibiting autophagy. These findings highlight the potential of EYA3 as a therapeutic target for GC, providing a foundation for future research and treatment strategies. Despite the promising data, the limitations of sample size and the need for further mechanistic studies are acknowledged.
胃癌（GC）是癌症相关死亡率的主要原因，其术后复发率高，长期生存状况不佳。Eyes Absent（EYA）蛋白家族在癌症进展中起着重要作用，EYA3 被认为可促进 GC 细胞增殖和肿瘤生长。我们利用 DepMap 数据库，鉴定出 EYA3 是 GC 中的一个感兴趣的基因。我们分析了 GC 组织和细胞系中的 EYA3 表达，进行了体外实验以评估其在细胞增殖中的作用，并进行了基因集富集分析以探讨其与自噬和 mTORC1 信号通路的关系。在体内，我们使用异种移植肿瘤模型来研究 EYA3 表达对肿瘤进展的影响。EYA3 在 GC 组织中持续上调，其高表达与患者生存率降低相关。在 GC 细胞系中沉默 EYA3 导致细胞增殖减少。观察到自噬抑制和 mTORC1 信号通路激活是 EYA3 促进 GC 细胞生长的机制。体内实验支持了体外实验的发现，显示 EYA3 表达降低时肿瘤生长较慢。本研究证实了 EYA3 在 GC 中的上调及其与不良预后的关联。EYA3 通过激活 mTORC1 信号通路和抑制自噬促进 GC 细胞增殖和肿瘤生长。这些发现强调了 EYA3 作为 GC 治疗靶点的潜力，为未来的研究和治疗策略提供了基础。尽管数据有前景，但也承认了样本量的限制和进一步的机制研究的需求。
