可药性
前列腺癌
癌症研究
翻译(生物学)
转移
小分子
癌症
生物
医学
内科学
信使核糖核酸
遗传学
基因
作者
Xiao Wang,Jiaxing Li,Yasheng Zhu,Ting Zeng,Jiayu Ding,Wenjian Min,Fei Huang,Shun-Qing Liang,Kai Yuan,Wenbin Kuang,Minghui Ji,Chengliang Sun,Hong‐Xun Yi,Liping Wang,Yuzhang Jiang,Haiping Hao,Yibei Xiao,Peng Yang
出处
期刊:Research Square - Research Square
日期:2021-09-21
被引量:1
标识
DOI:10.21203/rs.3.rs-879741/v1
摘要
Abstract Despite initial response to androgen signaling therapy, most prostate cancer (PCa) patients eventually relapse and remain incurable. ADAR1-mediated A-to-G editing plays oncogenic roles in various tumors. However, the specific function of ADAR1 and the global RNA edited targets governing PCa progression remain underexplored. Here, we demonstrate that highly expressed ADAR1 as a crucial oncogenic target in PCa, and develop a novel small-molecule ADAR1 inhibitor ZYS-1 with significant anti-tumor efficacy and favorable safety profile. Either depletion or pharmacological inhibition of ADAR1 dramatically suppress PCa growth, inhibit metastasis, and potentiate immune response. We further reveal that the translation of MTDH is repressed by ADAR1 in an editing-dependent manner, which drives cell proliferation and invasion in PCa. Collectively, these results shed light on ADAR1 as a novel druggable target in PCa therapy and highlight the widespread applicability of ADAR1 inhibitors for a broad spectrum of malignancies.
科研通智能强力驱动
Strongly Powered by AbleSci AI