In recent years, the involvement of E3 ubiquitin ligase constitutive photomorphogenesis 1 (COP1) in the tumorigenesis of gastric cancer (GC) has been elucidated. However, the exact underlying mechanism remains to be clarified. In the present study, the expression profiles of COP1 in GC were derived from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, followed by verification via immunohistochemical staining (IHC), Western blotting (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) reaction assays on clinical samples. In vitro, the gain- and loss-of-function experiments of COP1 protein were conducted to explore its role in GC cell lines HGC-27 and SGC-7901. Furthermore, we screened the interaction protein of COP1 by yeast two-hybrid experiment and verified their combination by co-immunoprecipitation (co-IP). We preliminary explored the possible underlying mechanisms of COP1 protein in GC cell lines via WB. COP1 was upregulated in GC tissues compared with the corresponding non-carcinoma tissues. In vitro, the upregulation of COP1 protein promoted the proliferation and migration of GC cells. The yeast two-hybrid experiment and co-IP indicated that Cadherin 18 (CDH18) could constitute a complex with COP1. Moreover, cells with COP1 over-expression showed low levels of CDH18 expression, with the intracellular PI3K/AKT pathway activated and the malignancy of GC cell lines enhanced. Our findings demonstrated that COP1 promoted the GC tumorigenesis by downregulated CDH18 with the involvement of PI3K/AKT signaling pathway in cell lines, suggesting the potential of COP1 as a prognostic biomarker and therapeutic target for GC.

中文翻译：

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COP1通过PI3K/AKT信号通路下调CDH18促进胃癌发生的作用

近年来，已经阐明了 E3 泛素连接酶组成型光形态发生 1 (COP1) 在胃癌 (GC) 肿瘤发生中的作用。然而，确切的潜在机制仍有待阐明。在本研究中，GC 中 COP1 的表达谱来源于基因表达综合 (GEO) 和癌症基因组图谱 (TCGA) 数据库，然后通过免疫组织化学染色 (IHC)、蛋白质印迹 (WB) 和定量验证临床样本的实时聚合酶链反应 (qRT-PCR) 反应测定。在体外，进行了 COP1 蛋白的功能获得和功能丧失实验，以探索其在 GC 细胞系 HGC-27 和 SGC-7901 中的作用。此外，我们通过酵母双杂交实验筛选了COP1的相互作用蛋白，并通过免疫共沉淀（co-IP）验证了它们的结合。我们通过 WB 初步探索了 GC 细胞系中 COP1 蛋白可能的潜在机制。与相应的非癌组织相比，COP1 在 GC 组织中上调。在体外，COP1蛋白的上调促进了GC细胞的增殖和迁移。酵母双杂交实验和 co-IP 表明钙粘蛋白 18 (CDH18) 可以与 COP1 构成复合物。此外，COP1 过表达的细胞显示出低水平的 CDH18 表达，细胞内 PI3K/AKT 通路被激活，GC 细胞系的恶性程度增强。