通过诱导Raf1/MST2介导的亡,DPY30敲击抑制结直肠癌的进展
HaiFeng Jiang1,2, WeiChao Su1,3, HaiXing Wang4
1Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian Province, China.
Heliyon
|February 5, 2024
概括
低调DPY30抑制结直肠癌细胞生长,并通过影响Raf1/MST2通路促进细胞亡. 这一发现为结直肠癌 (CRC) 提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 结肠直肠癌 (CRC) 因其高死亡率而构成重大全球卫生挑战.
- 基因组甲基转移酶复合体的核心亚单元DPY30在CRC病变发生中的确切作用在很大程度上仍未确定.
- 了解DPY30的功能对于开发针对CRC的新型治疗策略至关重要.
研究的目的:
- 研究DPY30在结直肠癌细胞亡中的作用和潜在机制.
- 为了阐明DPY30/Raf1/MST2信号轴在CRC进展和细胞存活.
主要方法:
- 在体外研究涉及DPY30在HT29和HCT116CRC细胞系中被淘汰.
- 评估细胞增殖,细胞亡率和与细胞亡相关的蛋白质的表达.
- RNA测序 (RNA-seq) 分析以确定DPY30的相互作用途径和作用因子,包括Raf1.
- 在体内实验使用裸体小鼠皮下异种移植和临床结肠直肠样本分析.
主要成果:
- 通过DPY30 Knockdown,显著抑制了CRC细胞的增殖,并增加了亡率.
- 低调DPY30促进了CRC细胞的亡,通过内源性编程死亡以酶依赖的方式.
- RNA-seq确定了DPY30和亡之间的联系,确定了Raf1作为潜在的效应因子.
- 通过DPY30抑制,通过通过H3K4me3修饰抑制Raf1转录活性,促进MST2诱导的亡.
- 在异种移植模型和临床CRC组织中,DPY30和Raf1表达水平显著相关.
结论:
- DPY30在调节结直肠癌细胞亡和扩散方面发挥着至关重要的作用.
- 信号轴DPY30/Raf1/MST2对于控制CRC细胞死亡和生存至关重要.
- 准DPY30/Raf1/MST2通路为早期诊断和结直肠癌的临床治疗提供了一个有希望的途径.
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