Downregulation of PHF19 inhibits cell growth and migration in gastric cancer
Downregulation of PHF19 inhibits cell growth and migration in gastric cancer
复制标题
PHF19的下调抑制胃癌细胞的生长和迁移
DOI：
10.1080/00365521.2020.1766555
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发表时间：
2020-05-21
影响因子：
1.9
通讯作者：
Xu, Zekuan
中科院分区：
文献类型：
--
作者：
Wang, Haixiao;Xu, Penghui;Xu, Zekuan
摘要目标：PHD指蛋白19（PHF 19）是多梳阻遏复合物2（PRC 2）的一个亚组分，与多种生物学过程相关。PHF 19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作用及其临床意义。方法：采用实时荧光定量PCR（qRT-PCR）和免疫组织化学方法检测PHF 19的表达。小干扰RNA和慢病毒颗粒沉默胃癌细胞中的PHF 19。然后通过CCK-8测定、集落形成和小鼠模型测量细胞生长。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PHF 19沉默的细胞、异种移植瘤和胃癌样品中的下游信号传导因子。结果如下：PHF 19在胃癌组织中的表达高于癌旁正常胃组织，且与肿瘤细胞分化程度和预后有关。在功能上，胃癌细胞中PHF 19的沉默导致细胞生长和迁移减少。稳定敲减PHF 19可抑制胃癌细胞在裸鼠模型中的致瘤性。Western blot结果显示，PHF 19下调后，磷酸化AKT和ERK水平降低，提示这两条信号通路可能介导了PHF 19的致癌作用。结论：PHF 19为胃癌的候选癌基因，为胃癌的治疗提供了一个新的潜在的药物靶点。
Abstract 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.