Objectives: The PHD Finger Protein 19 (PHF19), as a sub-component of polycomb repressive complex 2 (PRC2), has been identified to be associated with various biological processes. Aberrant expression of PHF19 has implicated in several cancer types. This study aims to investigate its function and clinical significance in gastric cancer for the first time.

Methods: The expression of PHF19 was evaluated by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. PHF19 was silenced by small interference RNAs and lentiviral particles in gastric cancer cells. Then cell growth was measured by CCK-8 assays, colony formation and in a mouse model. Transwell and wound healing assays were performed to detect cell migration. Western blot analysis was used to explore the downstream signaling factors in PHF19-silenced cells, xenograft tumors and gastric cancer samples.

Results: PHF19 was frequently upregulated in gastric cancer tissues compared with adjacent normal stomach tissues and this upregulation was correlated with tumor cell differentiation and poor outcome of gastric cancer patients. Functionally, the silencing of PHF19 in gastric cancer cells led to decreased cell growth and migration. Stable knockdown of PHF19 inhibited the tumorigenicity of gastric cancer cells in nude mice model. Western blot results demonstrated that phosphorylated AKT and ERK were reduced upon PHF19 downregulation, implying the two signaling pathways possibly mediate the oncogenic roles of PHF19.

Conclusions: We identified PHF19 as an oncogene candidate and provided a new potential drug target for gastric cancer.

目标： PHD手指蛋白19（PHF19）作为多梳抑制复合物2（PRC2）的子组件，已被确定与多种生物学过程相关。PHF19的异常表达与几种癌症类型有关。本研究旨在首次探讨其在胃癌中的功能及其临床意义。

方法：采用定量实时荧光定量PCR（qRT-PCR）和免疫组化方法检测PHF19的表达。胃癌细胞中的小干扰RNA和慢病毒颗粒使PHF19沉默。然后通过CCK-8测定，集落形成和在小鼠模型中测量细胞生长。进行Transwell和伤口愈合测定以检测细胞迁移。Western印迹分析用于探索PHF19沉默的细胞，异种移植肿瘤和胃癌样品中的下游信号传导因子。

结果：与邻近的正常胃组织相比，PHF19在胃癌组织中经常被上调，并且这种上调与胃癌患者的肿瘤细胞分化和不良预后有关。在功能上，胃癌细胞中PHF19的沉默导致细胞生长和迁移减少。PHF19的稳定敲低抑制了裸鼠模型中胃癌细胞的致瘤性。Western印迹结果表明，磷酸化的AKT和ERK在PHF19下调后减少，这意味着这两个信号通路可能介导PHF19的致癌作用。

结论：我们确定PHF19为致癌基因候选物，并为胃癌提供了新的潜在药物靶标。