通过刺激葡萄糖代谢重编程,HBx驱动肝癌干细胞的产生
Jinchen Liu1, Xueqin Wu1, Qiushi Yin1
1Key Laboratory of Tropical Translational Medicine, Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou, Hainan Province, PR China.
Journal of cellular and molecular medicine
|July 28, 2025
概括
肝细胞癌的复发与乙型肝炎病毒有关. 这项研究表明,乙型肝炎病毒x蛋白通过葡萄糖代谢变化驱动癌症干细胞的产生,突出显示HBx和PKM2作为治疗点.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 代谢工程是代谢工程.
背景情况:
- 肝细胞癌 (HCC) 的复发与乙型肝炎病毒 (HBV) 感染密切相关.
- 乙型肝炎病毒x蛋白 (HBx) 涉及肝细胞恶性转变和癌症异质性.
- 在HCC中驱动癌症干细胞 (CSC) 生成的代谢重编程中,HBx的具体作用尚不清楚.
研究的目的:
- 研究HBx诱导的葡萄糖代谢重编程如何促进HCC中CSC生成.
- 探索HBx,葡萄糖代谢和HCC的茎性之间的相互作用.
- 为了确定HCC治疗的潜在治疗点.
主要方法:
- 在HCC组织中对葡萄糖代谢酶和干性标记物的免疫组织化学分析.
- 西式涂抹,激光共聚焦显微镜和代谢检测套件用于分析蛋白质表达和代谢产品.
- 干细胞颗粒和软菌殖民地形成试验,以评估CSC的产生.
主要成果:
- 与相邻组织相比,HCC组织中PKM2,HK2,LDHA,CSC标记物 (CD133,CD44) 和HBx的显著增加表达.
- HBx上调关键的华堡效应酶和CSC标记物,而PKM2干扰减少了这些效应.
- 通过PI3K/AKT通路,PKM2与OCT4相互作用,调节其功能,并通过PI3K/AKT通路促进HCC的干性.
结论:
- 通过PI3K/AKT通路和PKM2激活,HBx通过重新编程葡萄糖代谢来促进HCC干和复发.
- PKM2对于启动HCC干细胞至关重要.
- 向HBx和PKM2为HCC提供了一个新的治疗策略.
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