Huang Yexiang, Zhu Yuyan, Zhang Zhe, Li Zhenhua, Kong Chuize
Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China.
Cancer Gene Ther. 2020 Dec;27(12):934-947. doi: 10.1038/s41417-020-0175-x. Epub 2020 May 6.
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.
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。