由YAP激活的NAT10通过激活酸路径促进肝细胞母细胞瘤的进展
Lingxiao Wang1, Shiguang Yang2, Jie Li3
1Department of General Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
International journal of biological sciences
|April 30, 2025
概括
由NAT10调节的N4-乙乙丁 (ac4C) 修饰驱动肝细胞瘤 (HB) 的生长. 抑制NAT10抑制了瘤的进展,揭示了这种儿科肝癌的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 肝母细胞瘤 (HB) 是最常见的儿科肝脏恶性瘤,治疗策略有限.
- 由N-乙转移酶10 (NAT10) 催化的N4-乙基提丁 (ac4C) 修饰与瘤发生有关,但其在HB中的作用尚不清楚.
研究的目的:
- 调查NAT10和ac4C修饰在肝细胞瘤发育和进展中的作用.
- 阐明NAT10在HB中的功能背后的分子机制.
- 评估NAT10作为HB的潜在治疗点.
主要方法:
- 在HB组织中分析NAT10表达.
- 在体外和体内实验涉及NAT10抑制的实验 (使用Remodelin).
- 研究YAP1/NAT10/G6PD信号轴及其对酸通路 (PPP) 的影响.
主要成果:
- 在HB中,NAT10显著上调.
- 抑制NAT10抑制了HB细胞的增殖和转移在体外和体内.
- YAP1/NAT10/G6PD通路增强PPP活动,促进HB生长和转移.
- 在HB模型中,雷莫德林有效地减弱了NAT10的瘤效应.
结论:
- 通过通过ac4C修饰调节G6PDmRNA稳定性,NAT10在肝细胞瘤中起着关键的致癌作用.
- YAP1/NAT10/G6PD轴是HB扩散和转移的关键驱动因素.
- 用像雷莫德林这样的抑制剂准NAT10为肝细胞瘤提供了一个有前途的治疗途径.
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