Wang Haixiao, Xu Penghui, Sun Guangli, Lv Jialun, Cao Jiacheng, Xu Zekuan
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of General Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.
Scand J Gastroenterol. 2020 Jun;55(6):687-693. doi: 10.1080/00365521.2020.1766555. Epub 2020 May 23.
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. 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. 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. We identified PHF19 as an oncogene candidate and provided a new potential drug target for gastric cancer.
PHD指蛋白19（PHF19）作为多梳抑制复合物2（PRC2）的一个亚组分，已被确定与多种生物学过程相关。PHF19的异常表达与多种癌症类型有关。本研究旨在首次探讨其在胃癌中的功能及临床意义。通过定量实时PCR（qRT-PCR）和免疫组织化学评估PHF19的表达。利用小干扰RNA和慢病毒颗粒在胃癌细胞中使PHF19沉默。然后通过CCK-8检测、集落形成实验以及在小鼠模型中检测细胞生长情况。进行Transwell实验和伤口愈合实验以检测细胞迁移。采用蛋白质免疫印迹分析来探究PHF19沉默细胞、异种移植瘤和胃癌样本中的下游信号因子。与相邻正常胃组织相比，PHF19在胃癌组织中经常上调，且这种上调与肿瘤细胞分化以及胃癌患者的不良预后相关。在功能上，胃癌细胞中PHF19的沉默导致细胞生长和迁移减少。在裸鼠模型中稳定敲低PHF19可抑制胃癌细胞的致瘤性。蛋白质免疫印迹结果表明，PHF19下调后磷酸化的AKT和ERK减少，这意味着这两条信号通路可能介导了PHF19的致癌作用。我们将PHF19鉴定为一种癌基因候选物，并为胃癌提供了一个新的潜在药物靶点。
