p53诱导circFRMD4A通过糖溶性重编程和cuproptosis抑制癌症的发展
Quan Liao1, Jun Deng2, Jing Tong3
1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China; Jiangxi Key Laboratory for Individual Cancer Therapy, Nanchang 330006, Jiangxi, China.
Molecular cell
|December 5, 2024
概括
瘤抑制器circFRMD4A重新编程癌细胞代谢,增强铜诱导的细胞死亡 (亡). 这条由p53调节的途径为野生型p53癌症提供了潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 代谢重编程 代谢重编程
背景情况:
- 质亡是一种由铜诱导的细胞死亡机制,影响线粒体代谢.
- 对于p53在cuproptosis中的作用及其与代谢重编程的联系尚未完全理解.
研究的目的:
- 调查循环RNAcircFRMD4A在p53介导的代谢重编程和cuproptosis中的作用.
- 阐明circFRMD4A影响癌细胞代谢和对cuproptosis敏感性的分子机制.
主要方法:
- 对circFRMD4A表达的分析及其通过p53和EWSR1.1的调节.
- 研究circFRMD4A和酸盐激酶M2 (PKM2) 之间的相互作用.
- 评估circFRMD4A对癌细胞细胞代谢和cuproptosis敏感性的影响.
- 在异种移植小鼠模型中评估p53激动剂和elesclomol的疗效.
主要成果:
- p53通过转录激活FRMD4A,从而形成抑制瘤的circFRMD4A.
- CircFRMD4A增强了癌细胞对埃莱斯克洛莫尔诱导的型亡的敏感性.
- 循环FRMD4A使PKM2失活,减少乳酸生产,并将糖解流转向TCA循环.
- 与p53激动剂和elesclomol的联合治疗抑制了体内瘤的生长.
结论:
- 通过circFRMD4A,p53促进了代谢重编程和cuproptosis.
- 通过调节癌细胞代谢,CircFRMD4A充当瘤抑制剂.
- 这项研究确定了一种结合p53激活和elesclomol用于野生类型p53癌症的新疗法策略.
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