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克里斯普尔查显示,RNA螺旋酶DDX41通过R-循环介导的RPL/RPS转录触发了核糖体生物发生和癌症进展

Hongquan Li¹, Yifei He¹, Jiawen Jiang¹

¹Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Nature communications

|August 11, 2025

概括

RNA螺旋酶DDX41通过增强核糖体生物发生和蛋白质合成来促进肝癌. 用同类哈林顿因 (HHT) 抑制蛋白质合成有效地减少了DDX41驱动癌症的瘤生长.

科学领域:

分子生物学分子生物学
在瘤学瘤学.
基因规则基因规则

背景情况:

RNA螺旋酶DDX41因其在抗病毒免疫力中的作用以及在髓状癌症中作为瘤抑制剂而得到认可.
它在固体瘤,特别是肝癌中的特定功能和意义尚不清楚.

研究的目的:

研究DDX41在固体瘤发育中的作用,并确定其在肝癌中的潜在机制.
探索针对肝癌中的DDX41的潜在治疗策略.

主要方法:

在体内进行CRISPR查,以识别促进瘤发生性的基因.
分析DDX41表达及其对R循环处理,基因转录和核糖体生物发生的影响.
对控制DDX41表达的调控因素 (KAT8,NR2C1/NR2C2) 的研究.
评估肝癌细胞对蛋白质合成抑制剂的敏感性和同类哈林顿因 (HHT) 治疗的疗效.

主要成果:

DDX41在固体瘤中高度表达,并驱动肝癌的进展.
DDX41通过促进R循环处理,加速RPL/RPS基因转录和增强核糖体生物生成来促进瘤发生性.
鉴定出KAT8和NR2C1/NR2C2是DDX41表达和促进体修饰的关键调节剂.
过度表达DDX41使肝癌细胞对蛋白质合成抑制剂敏感,HHT在临床前模型中显示出显著的瘤生长抑制.

结论:

DDX41在肝癌中起着瘤基因的作用,与其在髓状瘤中已知的瘤抑制作用不同.
针对蛋白质合成途径,特别是使用像HHT这样的抑制剂,对于具有DDX41表达升高的肝癌是一种有前途的治疗方法.

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