CDKN3高表达促进胃癌细胞的迁移和侵袭:基于调控p53/NF-κB信号通路和抑制胃癌细胞凋亡  

High expression of CDKN3 promotes migration and invasion of gastric cancer cells by regulating the p53/NF-κB signaling pathway and inhibiting cell apoptosis

作　　者：张毅 沈昱 万志强 陶嵩 柳亚魁 王栓虎 ZHANG Yi;SHEN Yu;WAN Zhiqiang;TAO Song;LIU Yakui;WANG Shuanhu(Department of Gastrointestinal Surgery,First Affiliated Hospital of Bengbu Medical University,Bengbu,Anhui 233030,China;Graduate School of Bengbu Medical University,Bengbu,Anhui 233030,China)

机构地区：[1]蚌埠医科大学第一附属医院胃肠外科,安徽蚌埠233030 [2]蚌埠医科大学研究生院,安徽蚌埠233030

出　　处：《南方医科大学学报》2025年第4期853-861,共9页Journal of Southern Medical University

基　　金：安徽省高校自然科学研究项目(KJ2020A0584)。

摘　　要：目的探究周期蛋白依赖性激酶抑制因子3(CDKN3)在胃癌中的表达情况,并分析其影响胃癌患者预后的潜在作用机制。方法纳入114例胃癌患者资料,分析CDKN3在胃癌组织中表达水平及其对胃癌患者术后5年生存率的影响;GO及KEGG富集分析预测CDKN3的生物学功能及可能的作用机制;通过慢病毒转染技术干预CDKN3的表达。采用Transwell、CCK-8、TUNEL染色、流式细胞术及Western blotting验证生物学功能。结果CDKN3在胃癌组织的表达水平显著高于癌旁组织(P<0.01),且CDKN3的表达水平与CEA、CA19-9、T分期及N分期相关(P<0.05)。单因素联合多因素分析显示,CDKN3高表达是影响胃癌患者术后5年生存率的独立风险因子(P<0.05)且CDKN3高表达对胃癌患者远期预后具有预判价值(P<0.01)。生物信息学富集分析提示CDKN3的功能可能与凋亡有关。Transwell实验结果显示,下调CDKN3可抑制胃癌细胞迁移、侵袭,上调则反之(P<0.01)。TUNEL染色结果显示,癌旁组织中细胞凋亡水平高于胃癌组织(P<0.01)。CCK-8和流式结果显示,降低CDKN3表达可抑制胃癌细胞的增殖,升高胃癌细胞凋亡率(P<0.05)。Western blotting结果显示过表达CDKN3后,p53、p21和促凋亡蛋白Bax表达降低,p-p65和抗凋亡蛋白Bcl-2表达升高(P<0.05)。结论CDKN3在胃癌组织中高表达并影响患者预后,其可能通过p53/NF-κB信号通路调控胃癌细胞凋亡并抑制其增殖、侵袭与迁移有关。Objective To investigate the expression of CDKN3 in gastric cancer and its impact on prognosis of gastric cancer patients.Methods We analyzed CDKN3 expression in clinical specimens from 114 gastric cancer patients and assessed its association with 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of CDKN3.The effects of lentivirus-mediated CDKN3 knockdown on biological behaviors of gastric cancer cells were evaluated using Transwell assay,CCK-8 assay,TUNEL staining,flow cytometry,and Western blotting.Results CDKN3 expression was significantly higher in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).High CDKN3 expression was an independent risk factor affecting 5-year postoperative survival of the patients and predictive for long-term prognosis(P<0.01).Enrichment analyses suggested a probable association of CDKN3 with apoptosis.In MGC-803 cells,CDKN3 knockdown significantly lowered migration and invasion capacities of the cells,while CDKN3 overexpression produced the opposite effects.TUNEL staining revealed a significantly lower level of cell apoptosis in gastric cancer tissues than in adjacent tissues(P<0.01).CDKN3 knockdown obviously inhibited proliferation and increased apoptosis of MGC-803 cells.CDKN3 overexpression down-regulated the expressions of p53,p21 and Bax and up-regulated the expressions of p-p65 and Bcl-2.Conclusion CDKN3 is highly expressed in gastric cancer tissues and affects patient prognosis.CDKN3 overexpression promotes proliferation,invasion and migration and suppressed apoptosis of gastric cancer cells possibly through the p53/NF-κB signaling pathway.

关 键 词：胃癌 CDKN3 凋亡 增殖 预后 p53/NF-κB 

分 类 号：R735.2[医药卫生—肿瘤]