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化特异性蛋白酶7通过稳定基本转录因子3来增强肝细胞癌的干性
Mingchao Hu1,2,3, Chengchen Dai1,2, Xieyin Sun1
1Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China.
Functional & integrative genomics
|February 10, 2024
概括
乌比基因化特异性蛋白酶7 (USP7) 通过稳定基本转录因子3 (BTF3) 来促进肝细胞癌 (HCC) 干和恶性瘤. 抑制USP7可以减少HCC细胞的增殖,迁移和自我更新.
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:
- 肝细胞癌 (HCC) 是一个主要的全球健康问题,预后不佳.
- 癌症干细胞 (CSCs) 驱动瘤开始,进展和HCC的治疗耐药性.
- 了解调节HCC干性的分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 阐明ubiquitination特定蛋白酶7 (USP7) 在调节肝细胞癌 (HCC) 的茎状性质中的作用.
- 确定USP7的目标,这些目标涉及维持HCC干细胞特征.
- 调查针对USP7在HCC中的治疗潜力.
主要方法:
- 使用USP7过度表达/敲击和USP7抑制剂P22077在HCC细胞系 (SK-Hep1, HepG2) 中进行了功能增益和功能丧失测定.
- 细胞增殖,迁移,入侵和自我更新使用CCK-8,殖民地形成,Transwell,痕和瘤球体测试进行了评估.
- 质谱学 (MS) 确定了潜在的USP7基质,并通过共免疫沉 (Co-IP) 验证了USP7和基本转录因子3 (BTF3) 之间的相互作用.
主要成果:
- USP7过度表达增强了HCC细胞的增殖,迁移,入侵,殖民地形成,上皮-介质细胞过渡 (EMT) 和干状性质.
- USP7 枯竭或抑制显著抑制了这些恶性表型和茎状特征.
- 质谱学确定BTF3是USP7基质;USP7与BTF3相互作用并稳定BTF3,而USP7的耗尽增加了BTF3的无处不在.
- 过度表达BTF3部分挽救了USP7耗尽对HCC恶性表型和干性的抑制作用.
结论:
- 通过稳定BTF3,USP7促进了HCC干细胞和恶性表型.
- 针对USP7代表了肝细胞癌的潜在治疗策略.
- 通过USP7调节BTF3是维持HCC干细胞特性的一个关键机制.
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