在METTL1驱动的TXNDC12表转录组增强增强了c-Myc稳定性,在HNSCC中通过USP5提高了c-Myc稳定性
Zizhao Mai1, Jiarong Zheng2, Ye Lu1
1Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
Experimental & molecular medicine
|August 1, 2025
概括
在头角状细胞癌 (HNSCC) 中,提升的硫素域含蛋白12 (TXNDC12) 通过稳定c-Myc.促进瘤生长和对西斯普拉丁的抗性. 针对这个METTL1-TXNDC12-c-Myc轴可能会改善HNSCC患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 头部和部状细胞癌 (HNSCC) 是一个重大的全球健康挑战.
- 了解HNSCC进展和治疗耐药性的分子驱动因素对于改善患者的治疗结果至关重要.
- 在HNSCC中硫素域含蛋白12 (TXNDC12) 的作用在很大程度上仍未被探索.
研究的目的:
- 调查TXNDC12在HNSCC进展和化学抵抗中的作用.
- 阐明TXNDC12在HNSCC中的功能背后的分子机制.
- 验证HNSCC.中TXNDC12通路的临床意义.
主要方法:
- 在HNSCC患者队列中分析TXNDC12表达.
- 在体外和体内调节TXNDC12水平.
- RNA转录组分析以确定下游的信号通路.
- 同免疫沉试验用于研究蛋白质与蛋白质相互作用.
- 评估METTL1在TXNDC12mRNA调节中的作用.
主要成果:
- 提升的TXNDC12表达与不良的临床结果和减少HNSCC的存活率相关.
- 减少TXNDC12减少了侵袭性瘤表型和西斯普拉丁耐药性;过度表达加剧了它们.
- TXNDC12的枯竭抑制了c-Myc的信号通路.
- 通过USP5相互作用,TXNDC12稳定了c-Myc蛋白,抑制了蛋白质体的降解.
- 通过一种依赖m7G的机制,METTL1增强了TXNDC12mRNA的稳定性.
结论:
- METTL1-TXNDC12-c-Myc轴是HNSCC进展和化学抵抗的关键调节器.
- TXNDC12通过USP5.5.通过稳定c-Myc促进了HNSCC的攻击性.
- 通过METTL1介导的TXNDC12表转录组调节有助于增强HNSCC中的c-Myc信号传递.
- 针对METTL1-TXNDC12-c-Myc通路代表了HNSCC的潜在治疗策略.
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