抑制PRMT5和CDK4/6导致黑色素瘤中具有独特的替代拼接模式
Lok Hang Chan1,2, Peihan Wang1,2, Shatha Abuhammad1,2
1Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
PloS one
|November 2, 2023
概括
循环素依赖性激酶4和6 (CDK4/6) 抑制剂对黑色素瘤细胞拼接的影响与蛋白质氨酸甲基转移酶5 (PRMT5) 抑制截然不同,揭示了独特的治疗途径.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症治疗方法 癌症治疗方法
背景情况:
- 循环素依赖性激酶4和6 (CDK4/6) 抑制剂在黑色素瘤治疗中表现有前途.
- 蛋白质氨酸甲基转移酶5 (PRMT5) 调节了CDK4/6.6下游的替代拼接.
- CDK4/6抑制对黑色素瘤剪接的确切影响及其对PRMT5的依赖性需要澄清.
研究的目的:
- 研究CDK4/6抑制对黑色素瘤拼接事件的全部影响.
- 确定这些拼接事件在多大程度上取决于PRMT5.5.
- 为了比较由CDK4/6和PRMT5抑制诱导的独特和常见的RNA剪接和基因表达特征.
主要方法:
- 在CHL1和A375黑色素瘤细胞系上使用全长mRNA测序.
- 用CDK4/6抑制剂palbociclib和PRMT5抑制剂GSK3326595.5治疗的细胞系
- 分析了差异性基因表达和差异性mRNA前剪接的数据.
主要成果:
- 抑制PRMT5导致基因表达和RNA剪接的变化比抑制CDK4/6更为广泛.
- 两种PRMT5和CDK4/6抑制共享共同的RNA拼接事件和基因表达特征.
- 大多数由CDK4/6抑制诱导的RNA拼接事件与由PRMT5抑制诱导的事件不同.
结论:
- CDK4/6可以独立于PRMT5.5调节替代拼接.
- 与PRMT5抑制相比,CDK4/6抑制导致不同的基因表达变化.
- 这些发现突出了CDK4/6和PRMT5抑制剂在黑色素瘤中的独特治疗机制.
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