NEDD4-1通过JAK2/STAT3通路促进胰腺癌上皮间质转化  

NEDD4-1 Promotes Epithelial-mesenchymal Transition of Pancreatic Cancer Through JAK2/STAT3 Pathway

作　　者：毕亭亭 刘通 夏天 刘岩 BI Tingting;LIU Tong;XIA Tian(Department of Gastroenterology,Xuzhou Central Hospital,Xuzhou Clinical School,Xuzhou Medical University,Jiangsu 221006,China)

机构地区：[1]徐州市中心医院消化内科、徐州医科大学徐州临床学院,221006 [2]徐州市中心医院普外科、徐州医科大学徐州临床学院,221006

出　　处：《医学研究杂志》2024年第11期132-138,共7页Journal of Medical Research

基　　金：江苏省徐州市卫生健康委医学科技创新资助项目(XWKYHT20230051);徐州医科大学附属医院优秀人才基金资助项目(XYFY202201)。

摘　　要：目的 探讨神经前体细胞发育下调蛋白4-1(neural precursor cell expressed, developmentally down-regulated 4-1, NEDD4-1)对人胰腺癌细胞生物学活性及上皮间质转化(epithelial-mesenchymal transition, EMT)的影响并探讨其机制。方法利用siRNA干扰技术下调BxPC-3细胞中NEDD4-1的表达水平,将实验分成对照组、空载体组(si-NC组)和NEDD4-1沉默组(si-NEDD4-1组)。实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction, RT-qPCR)法检测各组细胞NEDD4-1及EMT相关标志物mRNA的表达改变,MTT法评估各组细胞增殖活性,流式细胞术检测各组凋亡率,划痕实验及Transwell实验分析各组迁移和侵袭的活力,Western blot法检测各组NEDD4-1、EMT相关蛋白及JAK2/STAT3通路蛋白的表达改变。结果 与对照组和si-NC组比较,si-NEDD4-1组细胞中NEDD4-1、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)的mRNA及蛋白的表达显著下降(P<0.05),而E-钙黏蛋白(E-cadherin)的mRNA及蛋白的表达上调(P<0.05);si-NEDD4-1组细胞增殖、迁移及侵袭的活力受到抑制(P<0.05),而凋亡活性显著升高(P<0.05);si-NEDD4-1组p-JAK2及p-STAT3蛋白表达水平降低(P<0.05)。而对照组和si-NC组上述指标比较,差异均无统计学意义(P>0.05)。结论 NEDD4-1可能通过JAK2/STAT3通路促进胰腺癌细胞的EMT过程,进而调控细胞的增殖、凋亡、迁移及侵袭活性。Objective To investigate the effect of neural precursor cell expressed,developmentally down-regulated 4-1(NEDD4-1)on the biological activity and epithelial-mesenchymal transition(EMT)of human pancreatic cancer cells and the underlying mechanism.Methods The expression level of NEDD4-1 in the BxPC-3 cell line was down-regulated by siRNA interference technology.The experiment was divided into the control group,si-NC group,and NEDD4-1silencing group(si-NEDD4-1group).Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)method was used to detect the expression changes of NEDD4-1 and EMT-related markers mRNA in each group.The cell proliferation activity was evaluated by MTT assay,the apoptosis rate was detected by flow cytometry,the activity of migration and invasion was analyzed by scratch and transwell experiments,and the expression of NEDD4-1,EMT-related proteins,and JAK2/STAT3 pathway proteins were detected by Western blot.Results Compared with the control group and si-NC group,the mRNA and protein expressions of NEDD4-1,N-cadherin,and Vimentin in si-NEDD4-1group were significantly decreased(P<0.05),while the mRNA and protein expressions of E-cadherin were up-regulated(P<0.05).The proliferation,migration,and invasion of cells in the si-NEDD4-1group were inhibited(P<0.05),while the apoptosis activity was significantly increased(P<0.05).The expression levels of p-JAK and p-STAT3 protein in the si-NEDD4-1group were decreased(P<0.05).There was no significant difference in the above indicators between the control group and the si-NC group.Conclusion NEDD4-1 may promote the EMT process of pancreatic cancer cells through the JAK2/STAT3 pathway,and then regulate the proliferation,apoptosis,migration,and invasion activities of pancreatic cancer cells.

关 键 词：胰腺癌 NEDD4-1 上皮间质转化 迁移 JAK2/STAT3通路 

分 类 号：R735[医药卫生—肿瘤]