OTUB1 Promotes Progression and Proliferation of Prostate Cancer via Deubiquitinating and Stabling Cyclin E1.
OTUB1 Promotes Progression and Proliferation of Prostate Cancer via Deubiquitinating and Stabling Cyclin E1.
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OTUB1 通过去泛素化和稳定 Cyclin E1 促进前列腺癌的进展和增殖
DOI：
10.3389/fcell.2020.617758
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发表时间：
2020
影响因子：
5.5
通讯作者：
Jiang N
中科院分区：
文献类型：
--
作者：
Liao Y;Wu N;Wang K;Wang M;Wang Y;Gao J;Zhong B;Ma F;Wu Y;Jiang N
背景：前列腺癌（PCa）是目前世界范围内男性最常见的癌症。OTUB 1在多种肿瘤中发挥重要作用，与肿瘤增殖、迁移和临床预后密切相关。本研究旨在探讨OTUB 1对PCa增殖的调控作用及其机制。研究方法：使用TCGA数据库，我们确定OTUB 1在PCa中上调，并通过过表达或敲低OTUB 1在PC 3和C4-2细胞中观察到严重的功能变化。将异位肿瘤皮下植入裸鼠中，并对肿瘤组织进行IHC染色。通过Western印迹和免疫沉淀分析确定OTUB 1和cyclin E1之间的关系。结果：OTUB 1在PCa中的表达明显高于良性前列腺增生（BPH）。过表达OTUB 1可通过介导Cyclin E1的去泛素化而促进PC 3和C4-2细胞的增殖和迁移，而OTUB 1敲除则相反。裸鼠实验进一步解释了上述结论。我们最终确定OTUB 1通过去泛素化和稳定Cyclin E1促进PCa的增殖和进展。结论：我们的研究结果揭示了OTUB 1在PCa中的关键作用，OTUB 1通过去泛素化和稳定Cyclin E1促进PCa的增殖和进展。阻断OTUB 1/Cyclin E1轴或应用RO-3306可明显抑制PCa的发生和发展。OTUB 1/Cyclin E1轴可能为PCa的治疗提供一个新的潜在靶点。
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
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影响因子：
5.1
作者：
Bastos DA;Antonarakis ES
通讯作者：
Antonarakis ES
影响因子：
8
作者：
Ehedego H;Mohs A;Jansen B;Hiththetiya K;Sicinski P;Liedtke C;Trautwein C
通讯作者：
Trautwein C
影响因子：
11.2
作者：
Liu, Tong;Jiang, Le;Gu, Wei
通讯作者：
Gu, Wei
影响因子：
37.3
作者：
Iglesias-Gato D;Chuan YC;Jiang N;Svensson C;Bao J;Paul I;Egevad L;Kessler BM;Wikström P;Niu Y;Flores-Morales A
通讯作者：
Flores-Morales A
影响因子：
8
作者：
Altwaijry N;Somani S;Dufès C
通讯作者：
Dufès C