Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer
文献类型：期刊论文
| 作者 | Li, Xiao1,2; Li, Fei3; Ye, Fei4,5; Guo, Haotian; Chen, Wentao1,2; Jin, Jia; Wang, Yiran1; Dai, Pengfei2; Shi, Huili2,3; Tao, Hongru1 |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2023-07-25 |
| 卷号 | 42期号:7页码:24 |
| ISSN号 | 2211-1247 |
| DOI | 10.1016/j.celrep.2023.112798 |
| 通讯作者 | Gao, Dong(dong.gao@sibcb.ac.cn) ; Zhang, Yuanyuan() ; Luo, Cheng(cluo@simm.ac.cn) |
| 英文摘要 | In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC. |
| WOS关键词 | WEB SERVER ; ANDROGEN RECEPTOR ; GENE-EXPRESSION ; ALIGNMENT ; TARGET |
| 资助项目 | National Key Research and Development Program of China[2021ZD0203900] ; National Natural Science Foundation of China[81803554] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[32125013] ; National Natural Science Foundation of China[81803339] ; National Natural Science Foundation of China[21820102008] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020905] ; Research Funds of Hangzhou Institute for Advanced Study[2022ZZ01010] ; Research Funds of Hangzhou Institute for Advanced Study[ZYYCXTD-202004] ; Research Funds of Hangzhou Institute for Advanced Study[LG-QS-202206-01] ; High-level new Ramp;D institute[2019B090904008] ; Shanghai scientific and technological innovation action plan[2021B0909050003] ; Department of Science and Technology of Guangdong Province ; High-level Innovative Research Institute ; [23ZR1475100] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| 出版者 | CELL PRESS |
| WOS记录号 | WOS:001044403800001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306914]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Dong; Zhang, Yuanyuan; Luo, Cheng |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 5.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China 6.Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou 310018, Peoples R China 7.China Pharmaceut Univ, Nanjing 210009, Peoples R China 8.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xiao,Li, Fei,Ye, Fei,et al. Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer[J]. CELL REPORTS,2023,42(7):24. |
| APA | Li, Xiao.,Li, Fei.,Ye, Fei.,Guo, Haotian.,Chen, Wentao.,...&Luo, Cheng.(2023).Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer.CELL REPORTS,42(7),24. |
| MLA | Li, Xiao,et al."Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer".CELL REPORTS 42.7(2023):24. |
入库方式： OAI收割
来源：上海药物研究所
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