细胞核内液-液相分离作为抗肿瘤药物靶点的研究进展  

Research Progress on Targeting Nuclear Liquid-liquid Phase Separation for Developing Anti-tumor Drugs

作　　者：陈维浩 谭采薇 赵青威[2] 谢伟 CHEN Weihao;TAN Caiwei;ZHAO Qingwei;XIE Wei(College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;The First Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310003,China;The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,China)

机构地区：[1]浙江大学药学院,杭州310058 [2]浙江大学医学院附属第一医院,杭州310003 [3]浙江大学医学院附属第二医院,杭州310009

出　　处：《中国现代应用药学》2023年第12期1680-1686,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(82151216);浙江省重点研发计划项目(2021C01180)。

摘　　要：液-液相分离已被证明在细胞的基本生化途径中具有普遍的调控作用。最近的证据表明,液-液相分离失调是肿瘤发生和发展的重要驱动因素。通过揭示液-液相分离时空协调生物途径的作用机制,可以阐明肿瘤发生发展的分子基础,并开辟分子干预的新途径。本文概述了细胞核内液-液相分离现象的基本类型,以及其作为抗肿瘤药物靶标在组装超级增强子进行基因转录调控、激活核受体增强转录活性、调控RNA表观遗传以及驱动肿瘤发生等方面的作用。本文还以雄激素受体AR与核内m6A阅读器YTHDC1为例介绍了靶向干预液-液相分离相关候选药物的研究进展,以期为新药创制提供新思路。Liquid-liquid phase separation(LLPS)has been shown to have a universal regulatory role in the basic biochemical pathways of cells.Recent evidence suggests that LLPS dysregulation is an important driving factor in tumor initiation and progression.By revealing the mechanism of action of LLPS in coordinating biological pathways,the molecular basis of cancer initiation and progression can be elucidated,and new avenues for molecular intervention can be opened up.This article describes the basic types of nuclear LLPS and reviews their roles as anti-tumor drug targets in assembling super-enhancers for gene transcription regulation,enhancing nuclear receptors’transcription activity,regulating RNA epigenetics,and driving tumor initiation.The article also introduces the research progress of candidate drugs related to LLPS using examples such as androgen receptor AR and nuclear m6A reader YTHDC1,providing new ideas for drug development.

关 键 词：液-液相分离 抗肿瘤药物靶标 核内亚结构 雄激素受体 m6A阅读器YTHDC1 

分 类 号：R966[医药卫生—药理学]