NAP1L1通过E3泛酸酶UBR4调节BIRC2泛酸修饰,从而决定肝细胞癌的进展
Shi-Long Zhang1,2,3, Shen-Jie Zhang1,2, Lian Li4
1Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 550001, Guiyang, China.
核细胞组合蛋白1-like 1 (NAP1L1) 通过控制Baculoviral IAP重复含有2 (BIRC2) 通过UBR4.4通过ubiquitination控制肝细胞癌 (HCC) 的进展. 抑制NAP1L1可以抑制HCC的扩散,并促进细胞亡.
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:
- 核细胞组合蛋白1-like 1 (NAP1L1) 与肝细胞癌 (HCC) 的扩散有关.
- 在HCC中,还没有完全理解Baculoviral IAP重复含有2 (BIRC2) 稳定的调控机制.
- 在HCC恶性行为中NAP1L1的确切作用,如迁移,入侵和亡,需要澄清.
研究的目的:
- 研究NAP1L1在HCC细胞增殖,迁移,入侵和亡中的作用.
- 阐明NAP1L1影响BIRC2表达和HCC.稳定性的机制.
- 根据NAP1L1-BIRC2相互作用来确定HCC的潜在治疗点.
主要方法:
- 进行了细胞增殖试验,细胞亡试验,迁移试验和入侵试验.
- 用西式涂抹和定量实时PCR来评估蛋白质和基因表达.
- 协同免疫沉 (Co-IP) 试验,质谱学和无处不在试验被用来识别相互作用的蛋白质和机制.
- 动物模型被用来评估体内抗瘤效应.
主要成果:
- NAP1L1 knockdown 抑制了 HCC 细胞增殖和诱导细胞亡,但没有显著影响迁移或入侵.
- NAP1L1的敲击降低了BIRC2蛋白水平,但没有改变其mRNA水平,这表明了翻译后调节.
- UBR4被确定为一种E3泛素结合酶,它将NAP1L1与BIRC2联系起来,促进BIRC2泛化和降解.
- 在HCC组织中观察到BIRC2的高表达,与瘤进展相关.
结论:
- NAP1L1通过稳定BIRC2通过UBR4-介导的全方位化途径促进HCC的进展.
- 向NAP1L1可以通过促进BIRC2降解来抑制HCC的扩散和亡逃逸.
- 这项研究揭示了针对NAP1L1-UBR4-BIRC2轴的HCC新型治疗策略.
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