School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, PR China.
Jiangxi Institute of Respiratory Disease, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Pathol Res Pract. 2019 Oct;215(10):152592. doi: 10.1016/j.prp.2019.152592. Epub 2019 Aug 17.
Breast cancer is the most common malignant tumor among women in China, which seriously threatens women's physical and mental health. Tumorigenesis is closely related to the dysregulation of cell cycle. The cell cycle progression includes interphase and mitotic phase (M phase). Cyclin B1 is a key protein in regulating M phase, which is essential for the whole cell cycle progression. CyclinB1 can be degraded through ubiquitination mediated by the anaphase promoting complex/cyclosome (APC/C). However, the mechanism of how CyclinB1 is deubiquitinated in breast cancer still remains unclear. In this study, we discovered that CyclinB1 interacted with ubiquitin-specific peptidase 14 (USP14). Based on the deubiquitinating function of USP14, we detected the effect of USP14 on the ubiquitination of CyclinB1. Inhibiting the activity of USP14 or USP14 knockdown significantly increased the ubiquitination of CyclinB1. In accordance with this, knocking down USP14 arrested cell cycle at G2/M phase. Knocking down USP14 with siRNAs significantly inhibited the proliferation and migration of breast cancer cells. In conclusion, our study demonstrated that USP14 regulated the cell cycle of breast cancer cells by regulating the ubiquitination of CyclinB1, which will provide a solid theoretical basis for the development of anti-cancer drugs targeting USP14.
在中国，乳腺癌是女性中最常见的恶性肿瘤，严重威胁着女性的身心健康。肿瘤的发生与细胞周期的失调密切相关。细胞周期的进展包括间期和有丝分裂期（M 期）。细胞周期蛋白 B1 是调节 M 期的关键蛋白，对整个细胞周期的进展至关重要。细胞周期蛋白 B1 可以通过后期促进复合物/细胞周期蛋白（APC/C）介导的泛素化降解。然而，乳腺癌中细胞周期蛋白 B1 如何去泛素化的机制仍不清楚。在本研究中，我们发现细胞周期蛋白 B1 与泛素特异性肽酶 14（USP14）相互作用。基于 USP14 的去泛素化功能，我们检测了 USP14 对细胞周期蛋白 B1 泛素化的影响。抑制 USP14 的活性或敲低 USP14 显著增加了细胞周期蛋白 B1 的泛素化。与此一致，敲低 USP14 将细胞周期阻滞在 G2/M 期。用 siRNAs 敲低 USP14 显著抑制了乳腺癌细胞的增殖和迁移。总之，我们的研究表明，USP14 通过调节细胞周期蛋白 B1 的泛素化来调节乳腺癌细胞的细胞周期，这将为开发针对 USP14 的抗癌药物提供坚实的理论基础。
