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

BACKGROUND: 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 canc...

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Autores principales: Zhou, Zhengtao, Liu, Xiaoqiang, Li, Yulei, Li, Junhua, Deng, Wen, Zhong, Jian, Chen, Luyao, Li, Yu, Zeng, Xiantao, Wang, Gongxian, Zhu, Jingyu, Fu, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532081/
https://www.ncbi.nlm.nih.gov/pubmed/33061441
http://dx.doi.org/10.2147/OTT.S251830
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author Zhou, Zhengtao
Liu, Xiaoqiang
Li, Yulei
Li, Junhua
Deng, Wen
Zhong, Jian
Chen, Luyao
Li, Yu
Zeng, Xiantao
Wang, Gongxian
Zhu, Jingyu
Fu, Bin
author_facet Zhou, Zhengtao
Liu, Xiaoqiang
Li, Yulei
Li, Junhua
Deng, Wen
Zhong, Jian
Chen, Luyao
Li, Yu
Zeng, Xiantao
Wang, Gongxian
Zhu, Jingyu
Fu, Bin
author_sort Zhou, Zhengtao
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-75320812020-10-14 TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells Zhou, Zhengtao Liu, Xiaoqiang Li, Yulei Li, Junhua Deng, Wen Zhong, Jian Chen, Luyao Li, Yu Zeng, Xiantao Wang, Gongxian Zhu, Jingyu Fu, Bin Onco Targets Ther Original Research BACKGROUND: 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. Dove 2020-09-28 /pmc/articles/PMC7532081/ /pubmed/33061441 http://dx.doi.org/10.2147/OTT.S251830 Text en © 2020 Zhou et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhou, Zhengtao
Liu, Xiaoqiang
Li, Yulei
Li, Junhua
Deng, Wen
Zhong, Jian
Chen, Luyao
Li, Yu
Zeng, Xiantao
Wang, Gongxian
Zhu, Jingyu
Fu, Bin
TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells
title TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells
title_full TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells
title_fullStr TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells
title_full_unstemmed TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells
title_short TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells
title_sort tp53inp2 modulates epithelial-to-mesenchymal transition via the gsk-3β/β-catenin/snail1 pathway in bladder cancer cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532081/
https://www.ncbi.nlm.nih.gov/pubmed/33061441
http://dx.doi.org/10.2147/OTT.S251830
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