通过促进线粒体氧化酸化,SQLE驱动膀癌的进展
Yihong Dong1, Xinjian Jiang2,3, Xinxin Yang4
1NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Hospital of Harbin Medical University, Harbin, China.
Oncogene
|November 18, 2025
概括
胆固醇酶烯氧化酶 (SQLE) 通过增加线粒体活性氧物种 (mtROS) 来驱动膀癌 (BCa). 用terbinafine抑制SQLE显示了BCa治疗的希望.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 线粒体的新陈代谢
背景情况:
- 膀癌 (BCa) 的治疗选择有限.
- 胆固醇代谢在BCa中的作用尚未完全理解.
研究的目的:
- 研究烯环氧化酶 (SQLE) 在膀癌中的作用.
- 探索SQLE作为一个潜在的治疗目标.
主要方法:
- 在BCa患者中分析SQLE表达.
- 在体内研究使用膀特定的Sqle转基因和淘汰赛小鼠.
- 线粒体蛋白相互作用研究 (SQLE,LONP1,TFAM).
- 氧化酸化 (OXPHOS) 和线粒体活性氧物种 (mtROS) 的评估.
- 用Mito-TEMPO和terbinafine进行临床前治疗.
主要成果:
- SQLE在BCa上升调节,并且与生存率低下有关.
- SQLE过度表达加速了瘤的生长;淘汰赛抑制了它.
- 通过LONP1相互作用,SQLE稳定了TFAM,增加了OXPHOS和mtROS.
- 在临床前模型中,Mito-TEMPO和terbinafine抑制了瘤生长.
结论:
- 通过线粒体代谢重编程,SQLE是膀癌瘤发生的关键驱动因素.
- 针对SQLE使用像特比纳这样的抑制剂是BCa的潜在治疗策略.
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