USP40通过YAP/USP40正反循环促进肝细胞癌的进展
Huanye Mo1, Runtian Li1, Nan Yang2
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
乌比基特异性蛋白酶40 (USP40) 稳定了YES相关蛋白 (YAP),促进了肝细胞癌 (HCC) 的生长. 这种USP40-YAP反循环驱动HCC的进展,表明USP40是HCC的潜在治疗目标.
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:
- 是的相关蛋白 (YAP) 是肝细胞癌 (HCC) 进展的关键驱动因素.
- 无处不在蛋白质酶系统调节YAP的丰富性,但特定蛋白质酶的作用尚未完全理解.
研究的目的:
- 调查泛素特异蛋白酶40 (USP40) 在调节YAP稳定性的作用及其对HCC的影响.
- 阐明在HCC中USP40-YAP相互作用背后的分子机制.
主要方法:
- 同免疫沉以评估USP40-YAP相互作用.
- 在YAP上测定USP40的deubiquitinating活性.
- 在体外细胞测试 (增殖,殖民地形成,迁移,球形形成) 和体内HCC异种移植模型.
- RNA测序以分析基因表达变化.
- 对临床HCC患者数据的分析.
主要成果:
- USP40与YAP直接相互作用,并在特定位置 (K252,K315) 移除与K48相关的多基化,稳定YAP.
- USP40以依赖于YAP的方式促进HCC细胞的增殖,迁移和瘤生长.
- YAP通过转录上调USP40,形成一个积极的反循环.
- 在HCC组织中,USP40和YAP表达是正相关的,高USP40表明预后不佳.
结论:
- 在USP40和YAP之间有一个积极的反循环驱动HCC的进展.
- USP40稳定了YAP,增强了其在HCC中的致癌功能.
- USP40代表了肝细胞癌治疗的潜在治疗标.
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