通过双基因酶UCHL3介导稳定CTNNB1的激活促进了膀癌的进展
Tao Liu1, Meng-Qi Fan2, Xiao-Xiao Xie3
1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Journal of translational medicine
|September 22, 2023
概括
乌比奎丁C终端酶L3 (UCHL3) 通过激活Wnt信号通路来促进膀癌的生长和扩散. 准UCHL3为膀癌患者提供了一个有前途的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 丁β1基因 (CTNNB1) 在癌症恶性瘤中至关重要,过度活化与膀癌 (BCa) 发展有关.
- 乌比奎丁C终端化酶L3 (UCHL3),一种二化酶 (DUB),在癌症中表达异常.
- UCHL3被确定为膀癌中的新瘤基因,具有潜在的治疗标.
研究的目的:
- 研究UCHL3在膀癌进展中的作用.
- 阐明UCHL3影响膀癌发展的机制.
- 评估UCHL3作为膀癌的潜在治疗点.
主要方法:
- 使用CRISPR-Cas9技术创建具有UCHL3过度表达或淘汰的细胞系.
- 进行了细胞增殖,殖民地形成,软和Transwell迁移试验.
- 用RNA测序,西式斑点,共免疫沉,免疫光和体内小鼠模型来分析UCHL3的功能和机制.
主要成果:
- UCHL3过度表达增强了膀癌细胞的扩散,入侵和迁移.
- 在实验室和体内,UCHL3缺乏会延迟瘤生长,UCHL3缺乏的小鼠对膀瘤发生的敏感性降低.
- 发现UCHL3能够稳定CTNNB1,从而激活致癌的Wnt信号通路.
结论:
- 在膀癌中,UCHL3充当瘤促进剂,增强扩散,迁移和瘤发生.
- UCHL3稳定了CTNNB1,从而激活了Wnt信号通路,从而推动了膀癌的进展.
- UCHL3代表了膀癌的一个有前途的治疗标.
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