E3泛素连接酶和去泛素化酶在肝细胞癌中的研究进展  

Research Progress on E3 Ubiquitin Ligases and Deubiquitinating Enzymes in Hepatocellular Carcinoma

作　　者：武新翔 阮峥 侯孟森 李靖[3] 陈东东[3] 吕娟涛[3] 杨晓军 WU Xinxiang;RUAN Zheng;HOU Mengsen;LI Jing;CHEN Dongdong;LYU Juantao;YANG Xiaojun(First School of Clinical Medical,Gansu University of Chinese Medicine,Lanzhou 730000,China;Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province,Gansu Provincial Engineering Research Center for Prevention and Control of Gastrointestinal Malignancies,National Health and Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor,Lanzhou 730000,China;Gansu Provincial Hospital,Lanzhou 730000,China;The First Clinical School of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学第一临床医学院,甘肃兰州730000 [2]甘肃省外科肿瘤分子诊断与精准治疗重点实验室,甘肃省消化道恶性肿瘤防控工程研究中心,国家卫生健康委胃肠肿瘤诊治重点实验室,甘肃兰州730000 [3]甘肃省人民医院,甘肃兰州730000 [4]兰州大学第一临床医学院,甘肃兰州730000

出　　处：《肿瘤学杂志》2025年第1期59-65,共7页Journal of Chinese Oncology

基　　金：国家卫健委胃肠肿瘤诊治重点实验室博士基金项目(NHCDP2022001);博士研究生导师培育项目(ZX-62000001-2022-193);甘肃省卫生行业科研计划项目(GSWSKY2020-45);甘肃省卫生行业科研计划项目(GSWSKY2021-060);甘肃省自然科学基金(20JR10RA378);兰州市城关区科技计划项目(2023SHFZ0015)。

摘　　要：泛素-蛋白酶体途径(ubiquitin-proteasome pathway,UPP)是人体内蛋白质的主要降解途径,不同于其他致癌因子的作用机制,该途径导致肝细胞癌(hepatocllular carcinoma,HCC)进展的机制与泛素化和去泛素化酶失调有关。全文综述E3泛素连接酶和泛素特异性蛋白酶(ubiquitin specific peptidase,USP)家族成员在HCC发生及进展中的作用,包括E3泛素连接酶通过影响HCC增殖、迁移、侵袭、细胞周期、代谢重编程和耐药性等发挥双重作用,USP家族成员可通过介导HCC相关信号通路的激活、铁死亡抗性、耐药性、恶性表型,或与底物相互促进影响HCC进展,并阐明了相关作用机制,为今后开发潜在的HCC靶向生物药品提供借鉴,以期提高HCC远期治疗效果并改善预后。The ubiquitin-proteasome pathway(UPP)is the major protein degradation pathway in humans.In contrast to other oncogenic factors,the mechanism of UPP involving in hepatocellular carcinoma(HCC)progression is associated with dysregulation of ubiquitination and deubiquitination,in which ubiquitin E3 ligase and ubiquitin specific peptidase(USP)family play important roles.The E3 ubiqui-tin ligase has a dual role affecting HCC proliferation,migration,invasion,cell cycle,metabolic repro-gramming,and drug resistance.While USP family members influence HCC progression by mediating the activation of HCC-related signaling pathways,iron death resistance,drug resistance,malignant pheno-type,or reciprocal promotion with substrates.This paper elucidates the roles of E3 ligase and USP family in the occurrence and development of HCC and the relevant mechanisms,to provide reference for the development of potential HCC-targeted biological drugs.

关 键 词：肝细胞癌 泛素-蛋白酶体途径 E3泛素连接酶 去泛素化酶 

分 类 号：R735.7[医药卫生—肿瘤]