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在肺腺癌中,NRF2通过OTUD4调节EGF的稳定性

Shuming Hu¹, Yuan Yuan², Ruihan Yan¹

¹Department of Biochemistry & Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Biochemical and biophysical research communications

|March 22, 2024

概括

核因素红色素2相关因子2 (NRF2) 调节肺腺癌中的表皮生长因子 (EGF) 稳定性. NRF2激活了OTUD4,这使EGF脱和稳定,促进了瘤的进展.

科学领域:

分子生物学分子生物学
在瘤学瘤学.
基因规则基因规则

背景情况:

核因子红色素2相关因子2 (NRF2) 是一个转录因子,对细胞抗氧化反应和瘤进展至关重要.
NRF2影响各种细胞过程,包括新陈代谢和生物合成,其在肺腺癌 (LUAD) 中的作用是显著的.

研究的目的:

阐明NRF2调节肺腺癌表皮生长因子 (EGF) 稳定性的新机制.
调查duebiquitinases在NRF2-EGF调控途径中的作用.

主要方法:

在LUAD细胞中调节NRF2表达 (A549).
识别和分析EGF的无处不在状态.
预测和验证与NRF2.2相互作用的二维基丁酶 (OTUD4) 相互作用.
对NRF2与OTUD4促进体结合及其转录激活的分析.
在LUAD患者数据中对NRF2和OTUD4表达的相关性分析.

主要成果:

在LUAD细胞中,NRF2调节了EGF在蛋白质水平上的表达.
EGF被确定为一种无处不在的蛋白质,OTUD4与NRF2.2的相关性最高.
NRF2直接与OTUD4促进体结合,通过转录激活OTUD4的表达.
激活的OTUD4促进了EGF的脱氧化,并提高了EGF的稳定性.
在LUAD患者中观察到OTUD4和NRF2表达之间的显著相关性.

结论:

在肺腺癌中,NRF2通过双基因酶OTUD4提高了EGF的稳定性.
这一新的监管轴突出了LUAD治疗的潜在治疗目标.
这些发现揭示了一个新的机制,将NRF2,OTUD4和EGF与癌症进展联系起来.

关键词:

欧洲农业基金 (EGF) 提供.肺部腺癌瘤是肺部腺癌.这就是NRF2的NRF2.在OTUD4中,我们可以使用OTUD4.在Ubiquitination中使用.

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