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UNC5B通过与CDC14A和P53结合介导膀胱癌细胞的G2/M期阻滞。

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

作者信息

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

机构信息

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

出版信息

Cancer Gene Ther. 2020 Dec;27(12):934-947. doi: 10.1038/s41417-020-0175-x. Epub 2020 May 6.

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.

摘要

UNC5B是多种癌症中已知的肿瘤抑制基因。作为一种跨膜蛋白,UNC5B还以P53依赖的方式诱导细胞凋亡。在本研究中,我们通过质谱分析和生物信息学分析证明,UNC5B在膀胱癌细胞中通过G2/M期阻滞抑制增殖。通过与CDC14A和P53结合,UNC5B使P53在Ser-315位点去磷酸化。这种去磷酸化通过降低细胞周期蛋白B1的表达和增加p-CDK1的表达促进G2/M期阻滞,从而抑制肿瘤增殖。敲低CDC14A可抑制UNC5B在体外诱导的G2/M期阻滞,并消除UNC5B在体内对肿瘤增殖的抑制作用。我们的结果表明,UNC5B介导的细胞周期阻滞可能作为膀胱癌的一种潜在治疗方法。

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