单细胞转录组分析显示,在膀癌中,基因素乳酸和西斯普拉丁耐药性之间存在关联
Fei Li1, Henghui Zhang1, Yuan Huang1
1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China.
概括
乳化,特别是H3 lysine 18乳化 (H3K18la),通过激活基因转录来驱动膀癌 (BCa) 中的西斯普拉丁耐药性. 抑制H3K18la可以恢复对这种化疗的敏感性,提供新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 膀癌 (BCa) 往往会对基化疗产生抗性,例如西斯.
- 了解青抗性的分子机制对于改善治疗结果至关重要.
研究的目的:
- 为了研究乳化在膀癌中对西斯普拉丁耐药性的作用.
- 确定新的治疗点,以克服BCa.中的化疗耐药性.
主要方法:
- 单细胞RNA测序以分析BCa景观.
- 研究H3 lysine 18乳酸化 (H3K18la) 在基因转录中的功能.
- 评估H3K18la抑制对西斯普拉丁敏感性的影响.
主要成果:
- 鉴定出与糖解代谢相关的抗西斯普拉丁BCa细胞的一个子集.
- 发现H3K18la能够丰富促进子区域,激活目标基因.
- 向抑制H3K18la在耐药细胞中恢复了思丁的敏感性.
- 鉴定出YBX1和YY1是促进西斯普拉丁耐药性的关键转录因子.
结论:
- H3K18la是膀癌中西斯普拉丁耐药性的关键驱动因素.
- 准H3K18la及其下游因素提供了一种有希望的战略,以克服化学抵抗.
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