| 引用本文: | 陈维浩,谭采薇,赵青威,谢伟.细胞核内液-液相分离作为抗肿瘤药物靶点的研究进展[J].中国现代应用药学,2023,40(12):1680-1686. |
| CHEN Weihao,TAN Caiwei,ZHAO Qingwei,XIE Wei.Research Progress on Targeting Nuclear Liquid-liquid Phase Separation for Developing Anti-tumor Drugs[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(12):1680-1686. |
|
| 本文已被：浏览 3876次 下载 950次 |
码上扫一扫！ |
|
|
| 细胞核内液-液相分离作为抗肿瘤药物靶点的研究进展 |
|
陈维浩1,2, 谭采薇1, 赵青威2, 谢伟1,3
|
|
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
|
|
| 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。 |
| 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 |
| DOI：10.13748/j.cnki.issn1007-7693.20231485 |
| 分类号: |
| 基金项目:国家自然科学基金项目(82151216)；浙江省重点研发计划项目(2021C01180) |
|
| Research Progress on Targeting Nuclear Liquid-liquid Phase Separation for Developing Anti-tumor Drugs |
|
CHEN Weihao1,2, TAN Caiwei1, ZHAO Qingwei2, XIE Wei1,3
|
|
1.College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;2.The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China;3.The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
|
| Abstract: |
| 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. |
| Key words: liquid-liquid phase separation anti-tumor drug targets nuclear substructures androgen receptor m6A reader YTHDC1 |
