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泛素特异性蛋白酶24在恶性肿瘤进展中的研究
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Abstract:
泛素特异性蛋白酶24 (USP24)是一种关键的去泛素化酶，广泛参与蛋白稳态调控、细胞周期调节、DNA损伤修复、自噬、铁死亡及免疫调节等生物过程。近年来，USP24在膀胱癌、肺癌、急性淋巴细胞白血病(T-ALL)、肝细胞癌(HCC)及胃癌中的作用逐步被揭示，并被认为是影响肿瘤进展、侵袭及耐药性的关键分子。USP24通过去泛素化作用稳定GSDMB、PLK1、MCL-1、Beclin1和p300等关键蛋白，并激活STAT3、Notch1、IL-6及自噬–铁死亡通路，调控肿瘤细胞的增殖、代谢重编程及免疫逃逸。临床研究表明，USP24高表达与患者不良预后密切相关，可作为潜在的生物标志物用于评估疾病进展及治疗反应。此外，USP24小分子抑制剂(如WP1130、EOAI3402143和NCI677397)在体外及体内实验中展现出抗肿瘤潜力。尽管USP24靶向治疗仍面临特异性、药物递送及副作用等挑战，但其在精准医学中的应用前景值得进一步探索。未来研究应深入揭示USP24在不同癌种中的具体作用机制，并优化靶向抑制策略，为肿瘤治疗提供新思路。
Ubiquitin-specific protease 24 (USP24) is a deubiquitinating enzyme that plays a crucial role in various biological processes, including protein homeostasis, cell cycle regulation, DNA damage repair, autophagy, ferroptosis, and immune modulation. In recent years, the role of USP24 in multiple malignant tumors, such as bladder cancer, lung cancer, acute lymphoblastic leukemia, hepatocellular carcinoma, and gastric cancer, has been increasingly elucidated. USP24 has been identified as a key molecule influencing tumor progression, invasion, and drug resistance. Mechanistically, USP24 stabilizes critical proteins (e.g., GSDMB, PLK1, MCL-1, Beclin1, and p300) through deubiquitination, thereby activating pathways such as STAT3, Notch1, IL-6, and autophagy-ferroptosis. These regulatory mechanisms contribute to tumor cell proliferation, metabolic reprogramming, and immune evasion. Clinical studies have shown that high USP24 expression is closely associated with poor prognosis and may serve as a potential biomarker for assessing disease progression and treatment response. Moreover, research on USP24 as a therapeutic target is ongoing, with certain small-molecule inhibitors (e.g., WP1130, EOAI3402143, and NCI677397) demonstrating antitumor potential in both in vitro and in vivo studies. Despite challenges such as specificity, drug delivery, and potential side effects, USP24 holds significant promise in precision medicine. Future research should focus on elucidating the specific mechanisms of USP24 in different cancer types and optimizing targeted inhibition strategies to provide novel insights and approaches for cancer therapy.
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