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通过向p62-KEAP1-NRF2轴,TRIM39会加剧肝细胞癌的生长

Tianbao Yang¹, Zhigang Chen², Fang Yi¹

¹Department of Hepatobiliary Surgery, The First Affiliated Hospital, College of Clinical Medicine of Henan, University of Science and Technology, 471003, Luoyang , China.

Scientific reports

|December 20, 2025

概括

三方基因39 (TRIM39) 通过破坏p62的稳定,影响KEAP1-NRF2通路,促进肝细胞癌 (HCC) 细胞生长. 这一发现为HCC治疗提供了潜在的治疗点.

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:

三方基因 (TRIM) 蛋白质家族与瘤发生有关.
在肝细胞癌 (HCC) 中TRIM39的特定作用和机制尚不清楚.

研究的目的:

研究TRIM39在HCC中的生物功能和潜在机制.
为了确定TRIM39在HCC患者的预后意义.

主要方法:

对HCC组织中TRIM39表达的分析以及与患者预后的相关性.
在体外和体外功能研究,以评估TRIM39对HCC细胞增殖的影响.
涉及蛋白质与蛋白质相互作用的机制研究,泛化试验和途径分析 (TRIM39-p62-KEAP1-NRF2-HO-1轴).

主要成果:

在HCC组织中,TRIM39表达升高,与预后不佳有关.
TRIM39的过度表达增强了HCC细胞的增殖在体外和体内.
TRIM39促进了p62的无处不在,降低了p62的稳定性,随后通过KEAP1释放抑制了NRF2-HO-1通路.
恢复p62水平可以抵消TRIM39诱导的前瘤效应.

结论:

通过促进增殖,TRIM39在HCC中起着瘤基因的作用.
这项研究阐明了TRIM39-p62-KEAP1-NRF2轴作为HCC进展的关键机制.
TRIM39代表了HCC治疗的潜在治疗标.

关键词:

肝细胞癌是肝细胞癌.这就是NRF2的NRF2.P62 P62 是一个在 TRIM3939 中,在Ubiquitination中使用.

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