锌指蛋白883在胃癌组织中的表达及生物学功能  

Expression of zinc finger protein 883 in gastric cancer tissues and biological function

作　　者：张婷[1] 刘畅[2] 余钧辉[2] 赵伟[2] ZHANG Ting;LIU Chang;YU Junhui;ZHAO Wei(Department of Outpatient,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China;Department of General Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院门诊部,陕西西安710061 [2]西安交通大学第一附属医院普通外科,陕西西安710061

出　　处：《现代肿瘤医学》2023年第10期1854-1858,共5页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:82002547)。

摘　　要：目的:探讨锌指蛋白883(ZNF883)在胃癌组织中的表达及预后意义,并观察其对胃癌细胞增殖、迁移和侵袭的影响。方法:基于TCGA数据,通过GEPIA网络平台分析ZNF883 mRNA在胃癌组织和正常胃组织中的表达差异及其与患者生存率的相关性。通过蛋白免疫印记(Western blotting, WB)检测ZNF883蛋白在胃癌组织及对应癌旁组织中的表达水平。ZNF883 shRNA转染人胃癌细胞AGS和NCI-N87,WB检测敲低效率,CCK-8和Transwell小室检测细胞增殖、迁移和侵袭,并通过WB检测细胞周期蛋白D1(CCND1)、细胞周期依赖性激酶4(CDK4)和基质金属蛋白酶2/9(MMP2/9)蛋白表达。结果:TCGA数据分析发现ZNF883 mRNA在胃癌组织中的表达显著高于正常胃组织,其蛋白表达在胃癌组织中亦显著上调。生存分析证实ZNF883 mRNA高表达胃癌患者的无病生存率和总生存率均明显降低。敲低ZNF883显著抑制AGS和NCI-N87细胞增殖、迁移和侵袭。另外,敲低ZNF883显著减少胃癌细胞中CCND1、CDK4和MMP2/9蛋白水平。结论:ZNF883是一个新的胃癌驱动基因,胃癌组织中其高表达提示患者预后不良,ZNF883可能通过促进CCND1、CDK4和MMP2/9表达增强胃癌细胞增殖、迁移和侵袭。Objective:To explore the expression of zinc finger protein 883(ZNF883)in gastric cancer tissues and its prognostic significance,and observe its effects on the proliferation,migration and invasion of gastric cancer cells.Methods:Based on TCGA data,the GEPIA network platform was used to analyze the expression difference of ZNF883 mRNA between gastric cancer tissues and normal gastric tissues and its correlation with patient survival.The expression level of ZNF883 protein in gastric cancer tisues and corresponding tumor-adjacent tissues was detected by Western blotting(WB).ZNF883 shRNA was transfected into human gastric cancer cells AGS and NCI-N87 and the knockdown efficiency was detected by WB.CCK-8 and Transwell assays were used to detect cell proliferation,migration and invasion,and the protein expression of cyclin D1(CCND1),cyclin dependent kinase 4(CDK4)and matrix metallopeptidase 2/9(MMP2/9)was detected by WB.Results:TCGA data analysis found that the expression of ZNF883 mRNA in gastric cancer tissues was significantly higher than that in normal gastric tissues.ZNF883 protein level was also upregulated in gastric cancer tissues.Survival analysis demonstrated that gastric cancer patients with high ZNF883 mRNA expression had an obvious shorter disease-free survival and overall survival.ZNF883 knockdown prominently inhibited the proliferation,migration and invasion of AGS and NCI-N87 cells.In addition,ZNF883 knockdown markedly reduced the protein levels of CCND1,CDK4 and MMP2/9 in gastric cancer cells.Conclusion:ZNF883 is a novel gastric cancer driver gene.The high expression of ZNF883 in gastric cancer tissues indicates a poor prognosis for patients.ZNF883 may enhance the proliferation,migration and invasion of gastric cancer cells by promoting the expression of CCND1,CDK4 and MMP2/9.

关 键 词：胃癌 锌指蛋白883 预后不良 癌基因 

分 类 号：R735.2[医药卫生—肿瘤]