Gastric cancer (GC) is one of the most prevalent cancers and severely endangers human health. Due to the low rate of diagnosis, most patients with GC are diagnosed as advanced. CDC42 effector protein 3 (CDC42EP3) has been revealed to be involved in several types of human cancers' development and progression. However, the function of CDC42EP3 in GC is not yet clear. CDC42EP3 expression was detected by immunohistochemistry, quantitative real-time PCR and Western blot assay in tumor tissues and cell lines of GC. CDC42EP3 knockdown cell models were constructed by lentivirus transfection. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were evaluated by flow cytometry. Moreover, the mechanism was investigated by Human Apoptosis Antibody Array. The in vivo experiments were conducted to verify the effects of CDC42EP3 knockdown on the tumor growth of GC. The expression level of CDC42EP3 was up-regulated in tumor tissues. High CDC42EP3 expression was positively related to more advanced tumor grade. CDC42EP3 knockdown inhibited cell proliferation and migration, promoted cell apoptosis and suppressed the tumor growth. On the other hand, it was also found that the silencing of CDC42EP3 inhibited HSP27 and IGF-1sR expression as well as promoted Caspase3, p53, TNF-α, TNF-β, TRAILR-1 and TRAILR-2 expression. CDC42EP3 was revealed to work as a tumor promoter in the development and progression of GC, which could be a promising therapeutic target for the therapy of GC.

中文翻译：

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CDC42EP3 是参与胃癌发生发展的关键启动子。

胃癌（GC）是最常见的癌症之一，严重危害人类健康。由于诊断率低，大多数胃癌患者被诊断为晚期。CDC42 效应蛋白 3 (CDC42EP3) 已被证实参与多种类型的人类癌症的发展和进展。但CDC42EP3在GC中的作用尚不清楚。通过免疫组织化学、实时定量 PCR 和蛋白质印迹法检测肿瘤组织和 GC 细胞系中 CDC42EP3 的表达。通过慢病毒转染构建CDC42EP3敲低细胞模型。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定评估细胞增殖。伤口愈合试验和 transwell 试验被用来评估细胞迁移。还，流式细胞仪检测细胞凋亡和细胞周期。此外，通过人细胞凋亡抗体阵列研究了该机制。进行体内实验以验证CDC42EP3敲低对GC肿瘤生长的影响。CDC42EP3在肿瘤组织中的表达水平上调。CDC42EP3 的高表达与更晚期的肿瘤分级呈正相关。CDC42EP3敲低抑制细胞增殖和迁移，促进细胞凋亡并抑制肿瘤生长。另一方面，还发现CDC42EP3的沉默抑制了HSP27和IGF-1sR的表达，并促进了Caspase3、p53、TNF-α、TNF-β、TRAILR-1和TRAILR-2的表达。CDC42EP3 被揭示在 GC 的发展和进展中作为肿瘤促进剂起作用，