肝炎病毒感染驱动了人性化小鼠中的PSMB5-依赖性蛋白质酶激活和HBV相关的HCC
Ayse Tarbin Jannuzzi1,2, Gulce Sari2,3, Sema Arslan-Eseryel2
1Department of Pharmaceutical Toxicology, School of Pharmacy, Istanbul University, Istanbul 34116, Turkey.
Viruses
|November 27, 2025
概括
乙型肝炎病毒 (HBV) 感染通过在肝细胞中过度表达PSMB5亚单元来增加蛋白质酶活性. 这种失调与肝癌的发展和患者的不良预后有关.
科学领域:
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
背景情况:
- 肝细胞癌 (HCC) 是一种主要的肝癌,与乙型肝炎病毒 (HBV) 感染密切相关.
- 无素-蛋白酶体系统调节蛋白质降解,并与癌症有关,但其在与HBV相关的HCC中的作用尚不清楚.
- 在HBV感染和HCC期间,特定的蛋白质体子单元表达和活性需要进一步定义.
研究的目的:
- 调查HBV感染和HBV诱导的HCC中的蛋白质体子单元表达和活性.
- 为了确定蛋白质体mRNA表达和蛋白质体活性之间的关联.
- 为了揭示在乌比奎丁-蛋白酶体系统中的HBV特异性分子变化.
主要方法:
- 在HBV感染的人性化小鼠模型中分析蛋白质体子单元的mRNA表达特征.
- 功能性研究评估β5亚单元缺乏对MHC I水平和无处不在蛋白质积累的影响.
- 检查HBV感染患者肝脏中的β5mRNA/蛋白质水平和基米素类活性.
- 使用蛋白质阿特拉斯数据对β5mRNA表达与临床预后的相关性分析.
主要成果:
- 乙型肝炎病毒 (HBV) 感染始终过度表达基米素样活性 (β5) 蛋白酶子单元 (PSMB5).
- 缺少PSMB5会降低细胞表面MHC I,并增加无处不在的蛋白质积累,证实其在蛋白质体活动中的作用.
- 感染HBV的人类和小鼠肝脏显示PSMB5水平升高,并增强了基米托里类活性.
- 较高的PSMB5mRNA表达与肝细胞癌 (HCC) 患者的临床预后不佳相关.
结论:
- 乙型肝炎病毒感染通过增加PSMB5表达和肝细胞中的活性来显著改变蛋白酶体功能.
- 蛋白质体调节失调在与HBV相关的肝病理和肝细胞癌 (HCC) 的发展中起着关键作用.
- 向蛋白酶体动态为HBV相关的肝病和肝细胞癌 (HCC) 提供了潜在的治疗策略和生物标志物途径.
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