通过增强NOTCH1表达,N6-甲基氨酸阅读器YTHDF1促进肝细胞癌的干部和治疗抵抗
Xinyue Zhang1,2, Tianhong Su1,2, Yifan Wu2,3
1Department of Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
N6-甲基氨酸阅读器YTHDF1促进肝癌干细胞和耐药性. 向YTHDF1提供了一种有前途的治疗策略,通过增强对向疗法的敏感性来治疗肝细胞癌 (HCC).
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 在癌症中,N6-甲基氨酸 (m6A) RNA 修饰至关重要.
- 一个m6A读者YTHDF1与肝细胞癌 (HCC) 的进展有关.
- YTHDF1在HCC干性和耐药性中的作用需要进一步阐明.
研究的目的:
- 调查YTHDF1在HCC中的临床意义.
- 阐明YTHDF1影响HCC干性和耐药性的分子机制.
- 评估YTHDF1作为HCC的治疗点.
主要方法:
- 对人类HCC样本和患者衍生器官的分析.
- 在体内使用干细胞特异条件Ythdf1敲击小鼠的体内研究.
- 多原子分析包括RIP-seq,m6A-IP-seq,Ribo-seq和RNA-seq.
- 在体外测定使用HCC细胞系和脂质纳米粒子输送系统.
主要成果:
- 在HCC中,YTHDF1被上调,与高干度,复发和不良预后有关.
- YTHDF1促进癌症干细胞的更新和对伦瓦提尼布和索拉芬尼布的抵抗.
- YTHDF1直接与m6A修饰的NOTCH1mRNA结合,增强其稳定性和翻译性.
- 用脂质纳米颗粒向YTHDF1,在体内提高了向治疗的疗效.
结论:
- YTHDF1通过YTHDF1-m6A-NOTCH1表转录轴驱动HCC的干性和耐药性.
- YTHDF1是肝细胞癌的潜在治疗点.
- 抑制YTHDF1可以提高肝癌针对性治疗的敏感性.
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