eIF3d和eIF3e通过选择性翻译控制低氧,可以通过小分子抑制
Stephen C Purdy1, Kate Matlin2, Christopher Alderman3
1Department of Pharmacology, University of Colorado Anschutz Medical Campus (AMC), Aurora, CO, USA; Cancer Biology Program, University of Colorado Anschutz Medical Campus (AMC), Aurora, CO, USA.
Cell reports
|December 9, 2025
概括
低氧会通过真核细胞启动因子 (eIF) 3d/eIF3e引发翻译变化,影响癌症转移. 针对eIF3e可能会抑制压力诱导的翻译,并减少癌症的进展.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞应激反应的应激反应
背景情况:
- 缺氧促进细胞可塑性和转移,主要通过转录性变化.
- 缺氧期间的转化调节仍未得到充分研究.
- 低氧诱导因子 (HIFs) 调节对低氧的转录反应.
研究的目的:
- 研究急性缺氧中翻译控制机制.
- 确定真核细胞启动因子 (eIFs) 在缺氧反应中的作用.
- 确定抑制压力诱导的翻译和转移的治疗点.
主要方法:
- 核糖体概况分析在低氧期间的翻译.
- 评估了对eIF3d和eIF3e对低氧反应的依赖.
- 与乳腺癌患者的结果相关联的eIF3e副本数和表达.
- 选了针对eIF3e的小分子.
主要成果:
- 在急性缺氧中发现了依赖eIF3d/eIF3e的选择性翻译反应.
- 这种反应调节HIF1α的积累和细胞入侵.
- eIF3e副本数和表达与乳腺癌预后不佳相关.
- 在低氧和ER压力下发现了抑制eIF3e介导翻译的新型小分子.
结论:
- eIF3d/eIF3e在低氧反应中起着至关重要的作用.
- 针对eIF3e提供了一个潜在的策略来抑制压力诱导的翻译.
- 抑制eIF3e可能会降低癌症的可塑性和转移.
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