DLL3通过调节MAPK通路促进前列腺癌进展  

DLL3 promotes progression of prostate cancer through MAPK pathway

作　　者：李雨璇 于莉娜[3,4,5] 张韦洋 齐婧汝 赵卓扬 华兴 LI Yuxuan;YU Lina;ZHANG Weiyang;QI Jingru;ZHAO Zhuoyang;HUA Xing(Department of Pathology,School of Basic Medicine and Public Health,Jinan University,Guangzhou 510632,China;Departments of Pathology,Guangzhou Red Cross Hospital of Jinan University,Guangzhou 510220,China;Department of Pathology,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China;Department of Pathology,Nanfang Hospital,Guangzhou 510515,China;Guangdong Provincial Key Laboratory of Molecular Tumor Pathology,Guangzhou 510515,China)

机构地区：[1]暨南大学基础医学与公共卫生学院病理学系,广东广州510632 [2]暨南大学附属广州市红十字会医院病理科,广东广州510220 [3]南方医科大学基础医学院病理学系,广东广州510515 [4]南方医院病理科,广东广州510515 [5]广东省分子肿瘤病理学重点实验室,广东广州510515

出　　处：《中国病理生理杂志》2023年第12期2165-2175,共11页Chinese Journal of Pathophysiology

基　　金：Supported by Basic Research Project of Guangzhou High-Level University(No.2023A03J0606);Medical and Health Science and Technology Project of Guangzhou(No.20181A011025).

摘　　要：目的:探讨Delta样配体3(Delta-like ligand 3,DLL3)对前列腺癌进展的影响,并阐明其潜在的分子机制。方法:构建DLL3基因的过表达质粒和干扰质粒,通过功能实验评估DLL3对前列腺癌细胞增殖、迁移和侵袭能力的影响。采用裸鼠成瘤实验检测DLL3在体内对前列腺癌细胞PC-3增殖的影响。RNA测序检测过表达DLL3产生的差异基因并对其进行富集分析。Western blot检测DLL3对上皮-间充质转化(epithelial-mesenchymal transition,EMT)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路相关蛋白的影响。结果:与空载体组和空白对照组相比,DLL3过表达显著增强前列腺癌细胞的增殖、迁移、侵袭和EMT过程(P<0.05);而干扰DLL3表达则产生相反的效果(P<0.05)。此外,在裸鼠异种移植瘤模型中,DLL3上调可促进肿瘤生长(P<0.05)。进一步研究表明,DLL3上调导致MAPK信号通路中相关蛋白水平升高。有趣的是,MAPK抑制剂能够抑制由DLL3过表达引起的前列腺癌细胞增殖、迁移和侵袭(P<0.05)。结论:DLL3通过调节MAPK通路促进前列腺癌的增殖、迁移和侵袭。AIM:To explore the impact of Delta-like ligand 3(DLL3)on the progression of prostate cancer(PCa)and to elucidate its potential molecular mechanisms.METHODS:Overexpression and interference plasmids of DLL3 gene were constructed,and the effects of DLL3 on the proliferation,migration and invasion of PCa cells were assessed.Tumorigenesis assay was employed to determine whether DLL3 influenced the proliferation of PC-3 cells in vivo.The impact of DLL3 on epithelial-mesenchymal transition(EMT)and mitogen-activated protein kinase(MAPK)signaling was investigated through Western blotting.RESULTS:Overexpression of DLL3 significantly enhanced the proliferation,migration,invasion and EMT processes of PCa cells compared with empty vector group and blank control group(P<0.05).Conversely,knockdown of DLL3 expression yielded opposite effects(P<0.05).Moreover,up-regulation of DLL3 promoted tumor growth in the nude mouse xenograft model(P<0.05).Further investigation demonstrated that DLL3 upregulation led to increases in the levels of MAPK signaling pathway-related proteins.Interestingly,MAPK inhibitor effectively reduced the proliferation,migration and invasion of PCa cells caused by DLL3 overexpression(P<0.05).CON⁃CLUSION:DLL3 promotes the proliferation,migration and invasion of PCa through the MAPK pathway.

关 键 词：前列腺癌 Delta样配体3 上皮-间充质转化 MAPK通路 

分 类 号：R737.25[医药卫生—肿瘤] R363.2[医药卫生—临床医学]