eIF3i通过增强PHGDH转化促进结直肠癌细胞存活
Yaguang Zhang1, Xiaowen Wan2, Xuyang Yang1
1Department of Biotherapy, Cancer Center and State Laboratory of Biotherapy, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China; Research Laboratory of Cancer Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
The Journal of biological chemistry
|August 23, 2023
概括
细胞转化启动因子3子单元i (eIF3i) 通过促进PHGDH的转化,一个关键的代谢酶,驱动结直肠癌 (CRC) 的生长. 针对eIF3i和PHGDH可以抑制瘤的进展,揭示出一种新的癌症代谢调节途径.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 代谢重编程 代谢重编程
背景情况:
- 基因表达在转化层面受到严格的调节,调节失调与癌症发展有关.
- 细胞转化启动因子3子单元i (eIF3i) 与瘤生长有关,但其确切的机制尚不清楚.
- 大肠直肠癌 (CRC) 呈现出改变的基因表达模式,有助于瘤发生.
研究的目的:
- 阐明eIF3i在结直肠癌 (CRC) 进展中的作用和机制.
- 为了在CRC中在翻译水平上识别由eIF3i调节的基因.
- 为了研究eIF3i,PHGDH和癌症代谢之间的功能联系.
主要方法:
- 定量蛋白质组学和核糖体分析以识别eIF3i调节的基因.
- 在CRC细胞中进行基因淘汰实验 (eIF3i,PHGDH).
- 在体内瘤生长分析.
- 在PHGDHmRNA上对N6-甲基氨酸修饰的分析.
主要成果:
- eIF3i在CRC上升调节,促进细胞增殖.
- eIF3i可以选择性地增强PHGDH的翻译,PHGDH是血清蛋白合成中的关键酶.
- 通过METTL3介导的PHGDHmRNA的m6A修饰促进了eIF3i的结合和翻译.
- 抑制eIF3i或PHGDH可以在体内抑制CRC细胞增殖和瘤生长.
结论:
- eIF3i是结直肠癌中PHGDH转化的一个关键调节剂.
- eIF3i-PHGDH轴代表了癌症中代谢重编程的新机制.
- 向eIF3i为结直肠癌提供了一个潜在的治疗策略.
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