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乳酸化修饰新突破|南京医科大学研究团队揭示JOSD1驱动肝细胞癌恶性的机制

2026-05-10 22:24:38

乳酸化修饰新突破|南京医科大学研究团队揭示JOSD1驱动肝细胞癌恶性的机制

代谢重编程是肝细胞癌（HCC）的一个标志，使肿瘤能够快速生长和免疫逃逸。蛋白质翻译后修饰（PTM）串扰是细胞过程的关键调节因子；然而，其对HCC代谢重编程的贡献尚不清楚。阐明去泛素酶JOSD1在调节PTM串扰中的作用及其对HCC肿瘤糖酵解、进展和免疫治疗反应的影响。作者将多组学分析与细胞系、动物模型和患者样本的功能和机制研究相结合，以表征JOSD1及其在HCC中的下游通路。

2026年4月，南京医科大学研究团队在《Gut》杂志上发表了题为“JOSD1 drives hepatocellular carcinoma malignancy by modulating the ubiquitination-lactylation switch on PGAM1”的研究论文。

在这项研究中，JOSD1被确定为与糖酵解相关的基因，与不良预后相关。其过表达促进了恶性表型，并增强了糖酵解通量。从机制上讲，JOSD1-ARS1轴协同调节PGAM1 K251残基上的泛素化-乳酸化串扰。这种代谢转变损害了CD8+T细胞的浸润和功能，促进了免疫抑制。在治疗上，肝脏靶向抑制JOSD1有效地抑制了肿瘤进展，并与抗PD-1治疗协同作用，从而延长了生存期。JOSD1-ARS1轴调节PGAM1上的泛素化-乳酸化串扰，其中JOSD1充当关键的上游分子开关，驱动HCC中的代谢重编程和免疫逃逸。靶向JOSD1代表了一种有前景的治疗策略，可以调节肿瘤代谢并提高免疫治疗效果。

声明：本文整理参考文献:期刊年卷：Gut. 2026 Apr 28:gutjnl-2025-337331. doi: 10.1136/gutjnl-2025-337331. 如有侵权请联系后台删除，欢迎交流学习，转载需联系后台。

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SELECT * FROM `article` WHERE `id` < 548779 ORDER BY `id` DESC LIMIT 20,10 [ RunTime:0.003484s ]

0.154659s

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