通过ER应激反应,SPRTN参与肝细胞癌的发展
Anja Batel1, Mirjana Polović1, Mateo Glumac1
1Laboratory for Cancer Research, University of Split School of Medicine, Šoltanska 2, 21000, Split, Croatia.
Cancer gene therapy
|December 12, 2023
概括
SPRTN 蛋白质对于控制细胞内膜网膜压力至关重要,这是与肝癌有关的过程. 失去SPRTN功能加剧了ER压力,为肝细胞癌提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞应激反应的应激反应
背景情况:
- 由于蛋白质错误折叠而引起的内质网膜 (ER) 应激激活了未折叠蛋白质反应 (UPR),以维持细胞平衡.
- UPR功能障碍与肝细胞癌 (HCC) 的发展有关.
- SPRTN突变是已知的早期HCC的唯一遗传原因,但其作用尚不清楚.
研究的目的:
- 调查SPRTN在ER应激中的作用及其与肝细胞癌的联系.
- 阐明将SPRTN与HCC病变发生联系起来的分子机制.
主要方法:
- 在21个人类HCC组织中通过RT-qPCR,免疫斑块和免疫组织化学分析SPRTN和UPR标志物.
- 通过使用RNA测序,拉下测试,彗星测试和线粒体指数计算,评估SPRTN对SPRTN枯竭的HepG2细胞中ER应激的影响.
主要成果:
- 与SPRTN和UPR相关的基因/蛋白质表达在HCC样本中发生了改变.
- 发现SPRTN与UPR传感器GRP78相互作用.
- 在ER压力期间,SPRTN水平下降,而SPRTN枯竭使细胞对ER压力敏感.
结论:
- 在细胞对ER压力的反应中,SPRTN起着至关重要的作用.
- 这些发现揭示了SPRTN在ER恒温中的新功能,并为HCC病变发生提供了新的见解.
- 了解SPRTN的功能可能会导致改善HCC诊断和治疗策略.
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