线粒体UQCC3通过调节VEGF表达来控制胚胎和瘤血管生成
Guimin Zhang1, Binrui Liu1, Yun Yang1
1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
iScience
|August 4, 2023
概括
线粒体UQCC3对于血管形成 (血管生成) 是至关重要的. 它的缺失导致发育缺陷,并减缓瘤生长,突出其在癌症进展中的作用和作为治疗点的潜力.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 血管生物学 血管生物学
背景情况:
- 线粒体对血管生成至关重要,但根本的机制尚未完全理解.
- 识别血管生成的关键调节者对于理解发育和疾病至关重要.
研究的目的:
- 调查线粒体ubiquinol-cytochrome c减少酶复合组装因子3 (UQCC3) 在血管生成中的作用.
- 阐明UQCC3调节血管发育和瘤生长的分子机制.
主要方法:
- 在小鼠和斑马鱼模型中,TALEN介导的基因淘汰.
- 评估胚胎死亡率,血管发育和瘤生长.
- 分析反应性氧物种 (ROS) 生成,HIF-1α稳定性和低氧条件下的VEGF表达.
主要成果:
- 在小鼠和斑马鱼中,Uqcc3淘汰导致胚胎致死性和严重损害的血管化.
- 失去UQCC3显著降低了瘤生长和血管生成.
- 在缺氧下UQCC3的上调促进ROS生成,稳定HIF-1α,并增加VEGF表达.
结论:
- 在生理和病理上下文中,UQCC3是血管生成的关键调节者.
- UQCC3的表达与各种癌症的预后不佳相关,这表明它在瘤进展中的作用.
- UQCC3代表了抑制癌症血管生成的潜在治疗标.
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