TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells.
TP53INP2 Modulates Epithelial-to-Mesenchymal Transition via the GSK-3β/β-Catenin/Snail1 Pathway in Bladder Cancer Cells.
复制标题
TP53INP2通过GSK-3β/β-Catenin/Snail1通路调节膀胱癌细胞上皮向间质转化
DOI：
10.2147/ott.s251830
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发表时间：
2020
影响因子：
4
通讯作者：
Fu B
中科院分区：
文献类型：
--
作者：
Zhou Z;Liu X;Li Y;Li J;Deng W;Zhong J;Chen L;Li Y;Zeng X;Wang G;Zhu J;Fu B
肿瘤蛋白p53诱导核蛋白2（TP 53 INP 2）是一种自噬蛋白，对自噬体的形成至关重要。自噬的失调与多种人类疾病有关，包括癌症。本研究旨在探讨TP 53 INP 2在膀胱癌中的作用。实时定量聚合酶链反应检测mRNA水平。免疫组化和Western blot检测TP 53 INP 2蛋白的相对表达。采用CCK-8检测试剂盒和transwell法检测TP 53 INP 2基因沉默对膀胱癌细胞增殖、迁移和侵袭能力的影响。此外，进行转染和免疫荧光。在这项研究中，我们报告了TP 53 INP 2的高表达与膀胱癌患者的生存率低相关。结果表明，TP 53 INP 2的缺失抑制膀胱癌细胞的迁移、侵袭和上皮向间质转化（EMT）。探讨了其内在机制。结果表明，TP 53 INP 2敲低通过抑制活性非磷酸化β-连环蛋白和降低Snail 1水平来抑制EMT。此外，糖原合成酶激酶-3 β（GSK-3β）抑制剂IM-12消除了TP 53 INP 2沉默的作用。有趣的是，自噬的诱导部分消除了TP 53 INP 2敲低诱导的活性β-连环蛋白的减少以及对膀胱癌细胞中迁移和侵袭的抑制。总之，我们的结果表明，TP 53 INP 2的下调通过GSK-3β/β-catenin/Snail 1途径抑制膀胱癌中的EMT。本研究的发现揭示了TP 53 INP 2的新作用，并为膀胱癌的临床治疗提供了新的见解。
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. 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. 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. 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.