循环RNA编码的MET变体促进了质母细胞瘤瘤的产生
Jian Zhong1,2, Xujia Wu1,2, Yixin Gao1,2
1Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Nature communications
|July 25, 2023
概括
一种新型的MET变体,MET404,由循环METRNA (circMET) 编码,可以独立于HGF驱动质母细胞瘤瘤发生. 向MET404为质母细胞瘤患者提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 由肝细胞生长因子 (HGF) 激活的受体氨酸激酶MET对质母细胞瘤 (GBM) 至关重要,但针对HGF/MET的治疗效果有限.
- 这表明,在GBM病原发生过程中,MET信号传递机制未具特征.
研究的目的:
- 研究质母细胞瘤中MET信号传递的新机制.
- 为了识别和表征一种新的MET变体,涉及到GBM瘤发生.
主要方法:
- 对圆形METRNA (circMET) 和其编码蛋白变体MET404.4的分析.
- 在小鼠模型中进行基因操纵 (circMET 除,MET404 敲进,P53 敲出).
- 评估MET受体活性,GBM细胞行为和患者预后.
主要成果:
- 循环METRNA (circMET) 编码了一个404氨基酸MET变体 (MET404),它依赖于m6A阅读器YTHDF2.2.
- MET404形成了一个构成性活跃的MET受体,独立于HGF刺激.
- MET404表达驱动GBM瘤发生,与患者预后不佳相关.
- 用抗体或基因切除向MET404降低了GBM瘤性,显示了与MET抑制剂的结合性益处.
结论:
- 一种新的MET变种,MET404,促进质母细胞干细胞自我更新,侵入性和瘤性.
- MET404代表了质母细胞瘤的潜在治疗点,特别是在MET过度激活的情况下.
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