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.

中文翻译：

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UNC5B 通过与 CDC14A 和 P53 结合来介导膀胱癌细胞的 G2/M 期阻滞。

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 依赖性方式诱导细胞凋亡。在这项研究中，我们通过质谱和生物信息学分析证明 UNC5B 通过 G2/M 期阻滞抑制膀胱癌细胞的增殖。通过与 CDC14A 和 P53 结合，UNC5B 在 Ser-315 位点使 P53 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 的表达来促进 G2/M 期阻滞，从而抑制肿瘤增殖。CDC14A 的敲低在体外抑制了 UNC5B 诱导的 G2/M 期阻滞，并消除了 UNC5B 对体内肿瘤增殖的抑制作用。我们的研究结果表明，UNC5B 介导的细胞周期阻滞可能作为膀胱癌的潜在治疗方法。