ZFP36L1通过激活STAT3信号通路抑制上皮间质转化减弱人乳腺癌细胞的增殖、侵袭和迁移  

ZFP36L1 inhibits proliferation,invasion and migration of human breast cancer cells by inducing epithelial-mesenchymal transition through STAT3/p-STAT3 signaling pathway

作　　者：张烽萍 齐高秀 丁康 刘军[3] 陈敏[4] 林盟 周风华[1] ZHANG Fengping;QI Gaoxiu;DING Kang;LIU Jun;CHEN Min;LIN Meng;ZHOU Fenghua(Departnent of Clinical Pathology,Weifang Medical University,Weifang 261053,China;Department of Pathology,School of Clinical Medicine,Weifang Medical University,Weifang 261053,China;Emergency Surgery of Chinese Medicine Hospital of Gaomi,Weifang Medical University,Weifang 261053,China;Pathology Department of Affiliated Hospital,Weifang Medical University,Weifang 261053,China)

机构地区：[1]潍坊医学院临床病理系,山东潍坊261053 [2]潍坊医学院临床医学院病理科,山东潍坊261053 [3]潍坊医学院高密市中医院急诊外科,山东潍坊261053 [4]潍坊医学院附属医院病理科,山东潍坊261053

出　　处：《细胞与分子免疫学杂志》2022年第8期721-726,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：山东省自然科学基金(ZR2016HL20,ZR2020MH149);山东省医药卫生科技发展项目(2019WS606)。

摘　　要：目的探讨锌指蛋白36样分子1(ZFP36L1)在乳腺癌发生发展中的作用和机制。方法免疫组织化学方法检测乳腺癌组织ZFP36L1的表达和定位,分析ZFP36L1的表达与乳腺癌临床病理参数及预后的关系;MCF-7人乳腺癌细胞转染ZFP36L1过表达和空白质粒,通过5-乙炔基-2′-脱氧尿苷(EdU)和新型四唑氮盐(MTS)实验检测细胞增殖能力和细胞活性,Transwell^(TM)检测细胞的侵袭和迁移能力,Western blot法检测β联蛋白(β-catenin)、波形蛋白(vimentin)、上皮钙黏蛋白(E-cadherin)、信号转导子与转录激活子3(STAT3)和磷酸化STAT3(p-STAT3)蛋白水平。结果与高表达ZFP36L1的乳腺癌患者相比,低表达ZFP36L1患者肿瘤体积大,TNM分期高,淋巴结及远处转移率高;过表达ZFP36L1的MCF-7乳腺癌细胞的活性减低,增殖、侵袭和迁移能力降低,E-cadherin表达升高,β-catenin、vimentin表达降低;STAT3及p-STAT3表达升高。结论ZFP36L1作为一种抑癌基因,通过上皮间质转化(EMT)和STAT3信号通路抑制了乳腺癌增殖、侵袭和迁移。Objective To explore the role and mechanism of zinc finger protein 36 like 1(ZFP36L1)in breast cancer.Methods Sixty breast cancer patients were enrolled in the study.Immunohistochemistry was performed to evaluate the ZFP36L1 expression.Clinicopathological parameters were observed.MCF-7 cells were transfected with overexpressed ZFP36L1 plasmid.The viability of MCF-7 cells was assayed by the 5-ethynyl-2-deoxyuridine(EdU)and MTS assay.The invasion of MCF-7 cells was assessed by Transwell^(TM) assay.Western blot analysis was used to detect the expression ofβ-catenin,vimentin,E-cadherin,signal transducer and activator of transcription 3(STAT3),and phosphorylated STAT3(p-STAT3).ResultsZFP36L1-low expression has been found to be associated with poor prognosis in patients with breast cancer.Moreover,ZFP36L1 overexpression inhibited cell proliferation,invasion,migration,and epithelial-mesenchymal transition(EMT)in vitro.Accordingly,the expression of STAT3 and p-STAT3 increased significantly.Conclusion ZFP36L1,as a cancer suppressor gene,inhibits cell proliferation,invasion,and migration through EMT and STAT3 signaling pathway.

关 键 词：锌指蛋白36样分子1(ZFP36L1) 乳腺癌 细胞增殖 细胞侵袭 细胞迁移 上皮间质转化(EMT) 信号转导子与转录激活子3(STAT3) 

分 类 号：Q279[生物学—细胞生物学] R737.9[医药卫生—肿瘤] R392.11[医药卫生—临床医学] Q253