Li Junyan, Zhong Jinghua, Ye Jianming, Xiang Yi, Wang Xiangcai
The First Clinical Medical College, Gannan Medical University, Ganzhou, Jiangxi, China.
The Oncology Department of the First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China.
Front Oncol. 2025 Jul 2;15:1556011. doi: 10.3389/fonc.2025.1556011. eCollection 2025.
Ubiquitin-specific protease 39 (USP39), a member of the USP family, plays a unique role beyond classical deubiquitination by interacting with target molecules and regulating their pre-mRNA splicing, which enhances its functional specificity compared to other USP family members. Growing evidence highlights USP39's critical involvement in the progression of malignant tumors, where it acts as a pro-tumor factor, influencing cancer growth, proliferation, and metastasis. This paper provides a comprehensive review of the structure and functional mechanisms of USP39, emphasizing its role in regulating malignant tumor progression across various cancer types. Additionally, we explore the potential for developing targeted inhibitors based on USP39's regulatory functions, offering a theoretical framework for future drug development. Furthermore, the study examines USP39's contribution to resistance against antitumor therapies, highlighting its clinical relevance in advancing cancer treatment strategies. Despite the advances made, research on USP39-specific inhibitors remains limited. This work introduces a novel approach to designing inhibitors by leveraging USP39's functional and structural characteristics, paving the way for new therapeutic avenues in cancer research.
泛素特异性蛋白酶39（USP39）是USP家族的成员之一，它通过与靶分子相互作用并调节其前体mRNA剪接，在经典去泛素化作用之外发挥独特作用，与其他USP家族成员相比，这增强了其功能特异性。越来越多的证据表明，USP39在恶性肿瘤进展中起关键作用，它作为一种促肿瘤因子，影响癌症的生长、增殖和转移。本文全面综述了USP39的结构和功能机制，强调其在调节各种癌症类型的恶性肿瘤进展中的作用。此外，我们基于USP39的调节功能探索了开发靶向抑制剂的潜力，为未来药物开发提供了理论框架。此外，该研究考察了USP39对抗肿瘤治疗耐药性的影响，突出了其在推进癌症治疗策略方面的临床相关性。尽管取得了进展，但对USP39特异性抑制剂的研究仍然有限。这项工作引入了一种利用USP39的功能和结构特征设计抑制剂的新方法，为癌症研究中的新治疗途径铺平了道路。
