HDGF通过增强线粒体中反应性氧物种的产生来刺激肝脏瘤发生
Tsung-Hui Hu1, Jian-Ching Wu2, Shih-Tsung Huang3
1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
The Journal of biological chemistry
|October 12, 2023
概括
肝瘤衍生生长因子 (HDGF) 通过HDGF/核氨酸 (NCL) 途径增加活性氧物种 (ROS),从而促进肝癌,影响细胞能量和增殖.
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:
- 肝瘤衍生生长因子 (HDGF) 的过度表达和反应性氧物种 (ROS) 的积累与癌症进展有关.
- 在肝细胞癌 (HCC) 中HDGF和ROS之间的特定相互作用仍然不清楚.
研究的目的:
- 调查HDGF在ROS生成中的作用及其对肝癌发生的影响.
- 阐明HDGF诱导的HCC中ROS产生所涉及的信号通路.
主要方法:
- 在小鼠和培养的肝瘤细胞中,Orthotopic肝瘤模型.
- 在现场超氧化物检测,ROS检测光染料和流细胞计.
- 海马的代谢流量测试,抗氧化剂治疗和基因操纵 (敲击/突变).
主要成果:
- HDGF过度表达在肝瘤中显著提高了ROS水平.
- 再组合高密度脂肪酸 (rHDGF) 剂量依赖,增加了肝瘤细胞中的ROS产量和增强了线粒体生物能.
- 确定了HDGF/核素 (NCL) 轴作为HDGF诱导的ROS生成和瘤性行为的关键调解者.
结论:
- 通过NCL传递HDGF信号,刺激线粒体中的ROS生成,促进肝癌发生.
- 准高基和NCL通路可能为HCC提供治疗策略.
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