通过SRSF1介导的替代拼接,通过HIF1A/BNIP3/mitophagy轴调节膀癌的进展和对西斯普拉丁的敏感性
Qikai Wu1,2, Hao Yu1,2, Huanyou Sun1,2
1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Journal of translational medicine
|May 22, 2025
概括
在膀癌 (BCa) 中高SRSF1表达通过激活HIF1A/BNIP3/mitophagy通路来促进瘤进展和西斯普拉丁耐药性. SRSF1是BCa诊断和化疗的潜在生物标志物.
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:
- 替代拼接 (AS) 与瘤进展有关.
- 一个原型瘤基因SRSF1在剪接中起着关键作用.
- 在膀癌 (BCa) 进展和化学敏感性中SRSF1的作用尚不清楚.
研究的目的:
- 研究SRSF1在BCa进展中的功能.
- 确定SRSF1对BCa化学敏感性的影响.
- 阐明SRSF1在BCa中的作用背后的机制.
主要方法:
- 定量实时PCR (RT-qPCR) 和西部抹杀用于SRSF1表达.
- 在体外和体内测试扩散,迁移和瘤发生.
- RNA测序,JC-1染色和电子显微镜用于线粒的途径分析.
- 机械验证的RNA免疫沉降和CUT&RUN试验.
主要成果:
- 高SRSF1表达与不良的BCa预后相关.
- SRSF1促进BCa细胞的进展和对西斯普拉丁的抗性.
- 通过替代拼接,SRSF1增强了HIF1A的产生,激活了HIF1A/BNIP3/mitophagy轴.
- 这一轴驱动BCa的进展,并降低了西斯普拉丁的敏感性.
结论:
- 通过HIF1A/BNIP3/mitophagy通路,SRSF1促进BCa的进展和对西斯普拉丁的耐药性.
- SRSF1是BCa诊断和化疗反应的潜在生物标志物.
- 准SRSF1可能为BCa提供新的治疗策略.
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