Liao Yihao, Wu Ning, Wang Keke, Wang Miaomiao, Wang Youzhi, Gao Jie, Zhong Boqiang, Ma Fuling, Wu Yudong, Jiang Ning
Tianjin Institute of Urology. The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Key Laboratory of Breast Cancer Prevention and Therapy, State Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Hospital and Institute, Tianjin, China.
Front Cell Dev Biol. 2021 Jan 18;8:617758. doi: 10.3389/fcell.2020.617758. eCollection 2020.
Prostate cancer (PCa) is currently the most common cancer among males worldwide. It has been reported that OTUB1 plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis. The aim of this research is to investigate the regulatory effect of OTUB1 on PCa proliferation and the underlying mechanism. Using the TCGA database, we identified that OTUB1 was up-regulated in PCa, and observed severe functional changes in PC3 and C4-2 cells through overexpression or knock down OTUB1. Heterotopic tumors were implanted subcutaneously in nude mice and IHC staining was performed on tumor tissues. The relationship between OTUB1 and cyclin E1 was identified via Western blotting and immunoprecipitations assays. We found that the expression of OTUB1 in PCa was significantly higher than that in Benign Prostatic Hyperplasia (BPH). Overexpression OTUB1 obviously promoted the proliferation and migration of PC3 and C4-2 cells via mediating the deubiquitinated Cyclin E1, while OTUB1 knockout has the opposite effect. The nude mice experiment further explained the above conclusions. We finally determined that OTUB1 promotes the proliferation and progression of PCa via deubiquitinating and stabling Cyclin E1. Our findings reveal the critical role of OTUB1 in PCa, and OTUB1 promotes the proliferation and progression of PCa via deubiquitinating and stabilizing Cyclin E1. Blocking OTUB1/Cyclin E1 axis or applying RO-3306 could significantly repress the occurrence and development of PCa. OTUB1/Cyclin E1 axis might provide a new and potential therapeutic target for PCa.
前列腺癌（PCa）是目前全球男性中最常见的癌症。据报道，OTUB1在多种肿瘤中起关键作用，且与肿瘤增殖、迁移及临床预后密切相关。本研究旨在探讨OTUB1对PCa增殖的调控作用及其潜在机制。利用TCGA数据库，我们发现PCa中OTUB1表达上调，并通过过表达或敲低OTUB1观察到PC3和C4-2细胞发生严重的功能变化。将异位肿瘤皮下植入裸鼠体内，并对肿瘤组织进行免疫组化染色。通过蛋白质免疫印迹法和免疫沉淀试验确定OTUB1与细胞周期蛋白E1之间的关系。我们发现PCa中OTUB1的表达明显高于良性前列腺增生（BPH）。过表达OTUB1通过介导去泛素化的细胞周期蛋白E1明显促进PC3和C4-2细胞的增殖和迁移，而敲除OTUB1则产生相反的效果。裸鼠实验进一步解释了上述结论。我们最终确定OTUB1通过去泛素化和稳定细胞周期蛋白E1促进PCa的增殖和进展。我们的研究结果揭示了OTUB1在PCa中的关键作用，且OTUB1通过去泛素化和稳定细胞周期蛋白E1促进PCa的增殖和进展。阻断OTUB1/细胞周期蛋白E1轴或应用RO-3306可显著抑制PCa的发生和发展。OTUB1/细胞周期蛋白E1轴可能为PCa提供一个新的潜在治疗靶点。
