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泰姆斯通过KEAP1-NRF2途径增强结肠直肠细胞的抗氧化能力,抵抗铁亡

Jingtian Chen¹, Wei Wu¹, Lingxiao Wang¹

¹The Colorectal and Anal Surgery Department of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, China.

Journal of Cancer

|January 2, 2025

概括

胆固醇合成酶 (TYMS) 在结直肠癌 (CRC) 中被上调,通过KEAP1-NRF2通路增强细胞增殖和抗氧化能力. 这有助于抵抗ferroptosis,建议TYMS作为一个糟糕的预后标志物.

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:

乙基酸合成酶 (TYMS) 是DNA合成中的一个关键酶.
了解TYMS在结直肠癌 (CRC) 中的作用对于治疗策略至关重要.
TYMS,细胞抗氧化系统和铁亡之间的相互作用仍然是研究领域.

研究的目的:

阐明TYMS在结直肠癌中的生物效应和分子机制.
调查TYMS对CRC细胞增殖,抗氧化能力和铁灭菌耐药性的影响.
探索TYMS表达和CRC患者预后之间的关联.

主要方法:

西方斑块和免疫组织化学评估CRC组织中的TYMS表达.
进行MTT和殖民地形成试验,以评估TYMS对CRC细胞增殖的影响.
异种移植模型,代谢学,ROS检测和基因表达分析,以研究分子机制和铁灭.

主要成果:

与相邻的非癌性组织相比,CRC组织中的TYMS表达显著上调.
过度表达TYMS增强CRC细胞的增殖,并通过上调KEAP1-NRF2通路来增强细胞的抗氧化能力.
过度表达TYMS使得对埃拉斯诱导的铁亡产生抗性,而5-甲 (5-FU) 与埃拉斯具有协同效应.

结论:

在CRC中过度表达TYMS与患者预后不佳相关.
TYMS通过KEAP1-NRF2通路增强CRC细胞的抗氧化防御,促进对铁亡的抵抗力.
准TYMS可能是克服CRC中ferroptosis耐药性的治疗策略.

关键词:

结肠直肠癌是一种癌症.凯尔奇类的ECH相关蛋白 1 1 核因子红色素2相关因子2的核因子.这就是ROSOS ROS.甲基甲基酸合成酶是什么?铁性化 (ferroptosis) 是一种

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