eIF3d和eIF3e通过选择性翻译控制可以通过新型小分子抑制的低氧
bioRxiv : the preprint server for biology
|June 12, 2025
概括
缺氧会通过翻译引发细胞可塑性和转移,而不仅仅是转录. 针对eIF3e可以选择性地抑制这种应激反应,为癌症提供潜在的治疗途径.
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 (低氧) 促进癌细胞的可塑性和转移,主要是通过由缺氧诱导因子 (HIF) 介导的转录性变化.
- 在低氧期间的翻译调节,这在转录效应之前,仍然没有得到充分的研究.
- 翻译启动因子在低氧诱导的细胞反应中的作用在很大程度上尚未被探索.
研究的目的:
- 调查转化控制在急性缺氧反应中的作用.
- 为了确定参与低氧诱导的细胞可塑性和转移的特定转化因子.
- 探索针对缺氧诱导的翻译重编程的治疗策略.
主要方法:
- 核糖体简介分析急性缺氧期间的全球翻译变化.
- 功能性测试,以评估eIF3d/eIF3e对缺氧反应和癌细胞侵入的影响.
- 分析乳腺癌患者数据中的eIF3e表达和拷贝数.
- 小分子查以确定eIF3e介导翻译的抑制剂.
主要成果:
- 鉴定了对急性缺氧的选择性翻译反应,这取决于真核细胞启动因子3亚单元d (eIF3d) 和eIF3e.
- 这种eIF3d/eIF3e依赖的翻译控制了关键的低氧反应,包括HIF1a积累和细胞入侵.
- 提高eIF3e副本数和表达特征与乳腺癌患者的治疗结果较差相关.
- 发现针对eIF3e的新型小分子可以减少缺氧和ER压力诱导的翻译.
结论:
- 这项研究揭示了eIF3d/eIF3e在调解细胞对缺氧反应中的关键作用.
- 针对eIF3e是一个潜在的策略,可以抑制压力诱导的转化,可塑性和癌症转移.
- 这项工作强调了转化控制作为低氧驱动癌症进展的关键机制.
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