Mi Xingyu, Li Qingfeng, Long Guo, Pan Yilin, Xie Yulin, Lu Shiqi, Xiao Liang, Tang Jianing, Zhou Ledu
Department of Liver Surgery, Xiangya Hospital, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
Department of General Surgery, The Second Hospital of Liling City, Baitutang Town, Liling City, Zhuzhou City, Hunan 412207, China.
Int J Biol Sci. 2025 Jun 20;21(9):4270-4292. doi: 10.7150/ijbs.113193. eCollection 2025.
Ubiquitination is a reversible and dynamic process, precisely regulated by ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin ligases (E3), and deubiquitinating enzymes (DUBs). Dysregulation of DUBs disrupts the dynamic balance of ubiquitination, contributing to the development of various diseases, particularly cancer. An increasing number of studies have identified dysregulation of DUBs in various tumor types and have explored their regulatory mechanisms in these contexts. Hepatocellular carcinoma (HCC), the most common form of liver cancer, is highly malignant and has limited treatment options, necessitating the exploration of additional therapeutic strategies. Current research has identified dysregulation of DUBs in HCC, but their mechanisms of action remain poorly understood. Given the large number of DUB family members, there is significant potential for further investigation. This review summarizes the DUBs associated with HCC, including their structures, functions, and the mechanisms through which they regulate HCC development. Furthermore, we provide a brief overview of the discussed DUBs, aiming to offer new perspectives for future HCC research.
泛素化是一个可逆的动态过程,由泛素激活酶(E1)、泛素结合酶(E2)、泛素连接酶(E3)和去泛素化酶(DUBs)精确调控。DUBs的失调会破坏泛素化的动态平衡,导致各种疾病的发生,尤其是癌症。越来越多的研究已经确定了DUBs在各种肿瘤类型中的失调情况,并在这些背景下探索了它们的调控机制。肝细胞癌(HCC)是最常见的肝癌形式,具有高度恶性且治疗选择有限,因此有必要探索其他治疗策略。目前的研究已经确定了HCC中DUBs的失调情况,但其作用机制仍知之甚少。鉴于DUB家族成员众多,进一步研究具有很大潜力。本综述总结了与HCC相关的DUBs,包括它们的结构、功能以及调控HCC发展的机制。此外,我们简要概述了所讨论的DUBs,旨在为未来的HCC研究提供新的视角。