TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells

• Main Authors: Zhou Z, Liu X, Li Y, Li J, Deng W, Zhong J, Chen L, Zeng X, Wang G, Zhu J, Fu B
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: OncoTargets and Therapy
• Subjects: tp53inp2; β-catenin; snail1; emt; bladder cancer
• Online Access: https://www.dovepress.com/tp53inp2-modulates-epithelial-to-mesenchymal-transition-via-the-gsk-3b-peer-reviewed-article-OTT

Zhengtao Zhou,1,2,* Xiaoqiang Liu,1,2,* Yulei Li,1 Junhua Li,3 Wen Deng,1 Jian Zhong,4 Luyao Chen,1 Yu Li,1 Xiantao Zeng,5 Gongxian Wang,1,2 Jingyu Zhu,3 Bin Fu1,2 1Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Institute of Urology, Nanchang, People’s Republic of China; 3Department of Urology, Third Hospital of Hangzhou, Hangzhou, People’s Republic of China; 4Department of Surgery, Nankang District Chinese Medicine Hospital, Ganzhou, People’s Republic of China; 5Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin FuDepartment of Urology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel [phone]Email [e-mail] ZhuDepartment of Urology, Third Hospital of Hangzhou, 38 Westlake Road, Hangzhou, Zhejiang 310009, People’s Republic of ChinaTel [phone]Email [e-mail]: The tumor protein p53-inducible nuclear protein 2 (TP53INP2), an autophagy protein, is essential for autophagosome formation. The deregulation of autophagy is associated with multiple human diseases, including cancer. The present study aims to explore the role of TP53INP2 in bladder cancer.Materials and Methods: Quantitative real-time polymerase chain reaction was used to detect the mRNA level. Relative TP53INP2 protein expression was detected by immunohistochemistry and Western blot. The effect of TP53INP2 silencing on the proliferation, migration, and invasion of bladder cancer cells was investigated by CCK-8 detection kit and transwell assay. In addition, transfection and immunofluorescence were performed.Results: In this study, we report that high expression of TP53INP2 is correlated with poor patient survival in bladder cancer. Results demonstrate that the depletion of TP53INP2 inhibits the migration, invasion, and epithelial-to-mesenchymal transition (EMT) of bladder cancer cells. The underlying mechanism was explored. Results show that the TP53INP2 knockdown suppresses EMT by inhibiting the active non-phosphorylated β-catenin and decreasing the Snail1 levels. Furthermore, the glycogen synthase kinase-3 beta (GSK-3β) inhibitor IM-12 abrogates the effect of TP53INP2 silencing. Interestingly, the induction of autophagy partially abrogates the TP53INP2 knockdown-induced decrease in active β-catenin and inhibition of migration and invasion in bladder cancer cells.Conclusion: In summary, our results show that the downregulation of TP53INP2 inhibits EMT via the GSK-3β/β-catenin/Snail1 pathway in bladder cancer. The findings of this study uncover the novel role of TP53INP2 and offer new insights into bladder cancer clinical therapy.Keywords: TP53INP2, β-catenin, Snail1, EMT, bladder cancer