NEIL3调控AKT/GSK3β/Cyclin D1信号通路诱导肺腺癌细胞增殖  

NEIL3 induces the proliferation of lung adenocarcinoma cells via AKT/GSK3β/Cyclin D1 signaling pathway

作　　者：崔译文 赵燕 李明勇 李蓉 胡莹莹 CUI Yiwen;ZHAO Yan;LI Mingyong;LI Rong;HU Yingying(Department of Pathophysiology,Guangdong Medical University,Zhanjiang 524002,China)

机构地区：[1]广东医科大学病理生理学教研室,广东湛江524002

出　　处：《广东医科大学学报》2024年第5期449-455,共7页Journal of Guangdong Medical University

基　　金：国家自然科学基金青年项目(82102727);广东省医学科学技术研究基金项目(A2021243)。

摘　　要：目的探讨NEIL3(Nei核酸内切酶VIII样蛋白3)在肺腺癌组织中的表达,明确其对肺腺癌细胞增殖的影响和分子机制。方法免疫组化检测肺腺癌组织NEIL3的表达,分析NEIL3表达与患者临床病理参数和生存预后的关系。采用short hairpin RNA(shRNA)慢病毒载体转染技术干扰肺腺癌细胞A549中NEIL3的表达后,平板克隆实验、5-乙炔基-2′脱氧尿嘧啶核苷(EdU)实验和流式周期实验检测细胞增殖的改变;Western blot检测增殖相关分子Cyclin D1和信号通路AKT/GSK3β/β-catenin的改变。结果NEIL3表达与肺腺癌患者的临床分期、T分期及生存时间有关(P<0.05)。干扰NEIL3表达诱导A549细胞出现G0/G1期阻滞,抑制细胞增殖(P<0.05)。机制上,抑制NEIL3可促进Cyclin D1蛋白酶体降解从而下调其蛋白水平;干扰NEIL3可抑制AKT/GSK3β/β-catenin信号通路的激活(P<0.05)。结论NEIL3诱导肺腺癌细胞的增殖,机制可能与其调控AKT/GSK3β信号通路抑制Cyclin D1蛋白酶体降解有关。Objective The aim of this study is to investigate the expression and clinical significance of NEIL3(Nei like DNA glycosylase 3)in lung adenocarcinoma tissue,and to identify the effect of NEIL3 on the proliferation of lung adenocarcinoma cells and the underlying molecular mechanism.Methods Immunohistochemistry was used to detect the expression of NEIL3 in lung adenocarcinoma tissues,and the relationship between NEIL3 expression and the clinicopathological parameters,as well as the prognosis of patients were analyzed.After knockdown of NEIL3 expression in lung adenocarcinoma cell A549 through short hairpin RNA(shRNA),colony formation assay,5-ethynyl-2′-deoxyuridine(EdU)assay and flow cytometry were employed to detect the alterations in cell proliferation.Changes of proliferation-related molecules Cyclin D1 and AKT/GSK3β/β-catenin signaling pathway were detected by using Western blot.Results NEIL3 expression was correlated with clinical stage,T stage and the overall survival time of lung adenocarcinoma patients(P<0.05).Down-regulation of NEIL3 induced G0/G1 phase arrest in A549 cells and inhibited cell proliferation in vitro(P<0.05).Mechanically,inhibition of NEIL3 promoted the proteasomal degradation of Cyclin D1.Additionally,down-regulation of NEIL3 suppressed the activation of the AKT/GSK3β/β-catenin signaling pathway(P<0.05).Conclusion NEIL3 may promote the proliferation of lung adenocarcinoma cells through the activation of AKT/GSK3βsignaling pathway,which in turn inhibits the proteasomal degradation of Cyclin D1.

关 键 词：肺腺癌 NEIL3 细胞增殖 AKT/GSK3β/Cyclin D1信号通路 

分 类 号：R734[医药卫生—肿瘤]