UBXN1通过调节线粒体平衡稳定促进肝脏瘤发生
Kun Jiao1,2, Guiqin Xu2, Yun Liu2
1State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Journal of translational medicine
|May 21, 2024
概括
含有UBX域的蛋白1 (UBXN1) 通过维持线粒体平衡来促进肝癌. UBXN1与禁忌素 (PHB) 相互作用,其抑制导致线粒体损伤和癌细胞死亡.
科学领域:
- 线粒体生物学 线粒体生物学
- 癌症研究 癌症研究
- 肝细胞癌 (HCC) 的病原发生.
背景情况:
- 线粒体平衡对于瘤生长和生存至关重要.
- 将线粒体完整性与肝细胞癌 (HCC) 联系起来的分子机制尚未完全理解.
- UBX域含有蛋白1 (UBXN1) 的过活化与肝脏瘤发生有关.
研究的目的:
- 研究UBXN1在维护线粒体平衡中的作用.
- 阐明UBXN1影响肝脏瘤发生的分子机制.
- 为了确定UBXN1与HCC中的禁忌素 (PHB) 之间的相互作用.
主要方法:
- 利用使用睡眠美女 (SB) 转子子系统的瘤基因诱导的小鼠肝脏瘤模型.
- 在体外和体内使用殖民地形成,TUNEL和FACS试验评估HCC细胞生长.
- 采用共免疫沉 (Co-IP) 来研究UBXN1-PHB相互作用,并分析了LIHC数据集的UBXN1表达.
主要成果:
- 在人类HCC和小鼠肝脏瘤中,UBXN1被上调,与患者的生存率差相关.
- UBXN1促进HCC细胞生长和肝脏瘤发生,特别是在NRas/c-Myc或c-Myc/shp53驱动的模型中.
- UBXN1与禁忌素 (PHB) 相互作用,维持其表达并维持线粒体平衡;UBXN1抑制导致线粒体损伤和亡.
结论:
- UBXN1与PHB相互作用,在肝脏瘤发生过程中促进线粒体平衡.
- UBXN1是肝癌发展和进展的关键因素.
- 准UBXN1可能为HCC提供治疗策略.
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