E3泛素连接酶在宫颈癌中的研究进展

doi:10.12280/gjfckx.20250173

摘要/Abstract

摘要：

宫颈癌是妇科常见的恶性肿瘤，发病率和死亡率均较高且呈年轻化趋势，严重危害女性健康。高危型人乳头瘤病毒（human papilloma virus，HPV）持续感染是宫颈癌发生发展的关键和始动因素，尽管手术和放化疗等使宫颈癌患者的预后获得了很大改善，但晚期宫颈癌生存率仍不容乐观，因此，寻找针对性的治疗靶点可为临床诊治提供新方法。E3泛素连接酶作为泛素化级联反应中的关键酶，负责将泛素分子标记到靶蛋白上，从而调控其生物学功能。E3泛素连接酶主要可分为RING型、HECT型及RBR型三大类，通过调控宫颈癌细胞的增殖、参与迁移与侵袭、影响细胞周期、调节放化疗敏感性和介导免疫逃逸等机制阻断HPV持续感染状态，抑制宫颈癌进展。在应用方面，采用蛋白酶体抑制剂或直接靶向E3泛素连接酶均能够延缓疾病进展，且近年新开发的蛋白降解靶向嵌合体及分子胶也在治疗领域展现出广阔前景。

关键词: 泛素化, 泛素蛋白连接酶类, 宫颈肿瘤, 治疗, 人乳头瘤病毒

Abstract:

Cervical cancer is the common gynecological malignancy with a relatively high incidence and mortality rate, and it shows a trend of younger onset, seriously endangering women′s health. Persistent infection with high-risk human papilloma virus (HPV) is the key and initiating factor for the occurrence and development of cervical cancer. Although surgery, radiotherapy, and chemotherapy have greatly improved the prognosis of cervical cancer patients, the survival rate of advanced cervical cancer remains unsatisfactory. Therefore, finding targeted therapeutic targets can provide new methods for clinical diagnosis and treatment. As a key enzyme in the ubiquitination cascade reaction, E3 ubiquitin ligases is responsible for tagging ubiquitin molecules onto target proteins, thereby regulating their biological function. E3 ubiquitin ligases can be mainly divided into three major categories: RING-type, HECT-type, and RBR-type. They can block the persistent HPV infection state and inhibit the progression of cervical cancer through mechanisms such as regulating the proliferation of cervical cancer cells, participating in cell migration and invasion, affecting the cell cycle, regulating the sensitivity to radiotherapy and chemotherapy, and mediating immune evasion. In terms of application, using proteasome inhibitors or directly targeting E3 ubiquitin ligases can delay the progression of the disease. In recent years, newly developed proteolysis, targeting chimeras and molecular glues also show broad prospects in the field of treatment.

Key words: Ubiquitination, Ubiquitin-protein ligases, Uterine cervical neoplasms, Therapy, Human papilloma virus

连思晗, 韩梦菲, 王玉珏, 赵琳燕, 胡燕. E3泛素连接酶在宫颈癌中的研究进展[J]. 国际妇产科学杂志, 2025, 52(3): 319-325.

LIAN Si-han, HAN Meng-fei, WANG Yu-jue, ZHAO Lin-yan, HU Yan. Research Progress on E3 Ubiquitin Ligases in the Cervical Cancer[J]. Journal of International Obstetrics and Gynecology, 2025, 52(3): 319-325.

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