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UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53

Cancer Gene Therapy volume 27, pages 934–947 (2020)Cite this article

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A Correction to this article was published on 20 October 2021

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Abstract

UNC5B is a known tumor suppressor gene in a variety of cancers. As a transmembrane protein, UNC5B also induces apoptosis in a P53-dependent manner. In this study, we demonstrate that UNC5B inhibits proliferation through G2/M phase arrest by mass spectrometry and bioinformatics analysis in bladder cancer cells. By combing with CDC14A and P53, UNC5B dephosphorylated P53 at Ser-315 site. This dephosphorylation facilitated G2/M phase arrest by reducing the expression of cyclin B1 and increasing the expression of p-CDK1, thus inhibiting tumor proliferation. Knockdown of CDC14A suppressed the G2/M phase arrest induced by UNC5B in vitro, and eliminated the inhibitory effect of UNC5B on tumor proliferation in vivo. Our results show that UNC5B-mediated cell cycle arrest may act as a potential treatment for bladder cancer.

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Fig. 1: The impact of full-length UNC5B and UNC5B truncates on the proliferation of 5637 and T24 cells.
Fig. 2: Full-length UNC5B induced G2/M phase arrest in 5637 and T24 cells.
Fig. 3: CDC14A was closely related to G2/M phase arrest in 5637 and T24 cells.
Fig. 4: UNC5B dephosphorylated P53 at Ser-315 site by combing with CDC14A and P53, thereby mediating cell cycle arrest and inhibit proliferation.
Fig. 5: Knockdown of CDC14A suppressed the G2/M phase arrest induced by UNC5B.
Fig. 6: Knockdown of CDC14A eliminated the inhibitory effect of UNC5B on tumor proliferation in mice.

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Acknowledgements

This work was supported by National Natural Science Fund [Grant No. 81672525], the Project of Distinguished Professor of Liaoning Province (Grant No. [2012]145), Liaoning Natural Science Fund [Grant No. 201602830], Shenyang clinical medicine research center (Grant No. [2017]76) and Shenyang Plan Project of Science and Technology/Shenyang Science and Technology Bureau (Grant No. F17-230-9-08), China Medical University’s 2017 discipline promotion program (Grant No. 2017XK08), China Medical University’s 2018 discipline promotion program.

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  1. Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China

    Yexiang Huang, Yuyan Zhu, Zhe Zhang, Zhenhua Li & Chuize Kong

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Correspondence to Chuize Kong.

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Huang, Y., Zhu, Y., Zhang, Z. et al. UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53. Cancer Gene Ther 27, 934–947 (2020). https://doi.org/10.1038/s41417-020-0175-x

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