NEDD4-1 Promotes Epithelial-mesenchymal Transition of Pancreatic Cancer Through JAK2/STAT3 Pathway
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 mecha-nism.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 NEDD4-1 silencing group(si-NEDD4-1 group).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-NEDD4-1 group 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-NEDD4-1 group were inhibited(P＜0.05),while the apoptosis activity was sig-nificantly increased(P＜0.05).The expression levels of p-JAK and p-STAT3 protein in the si-NEDD4-1 group 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 prolifera-tion,apoptosis,migration,and invasion activities of pancreatic cancer cells.
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