Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication.
Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication.
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抑制 N-乙酰转移酶 10 通过调节 DNA 复制抑制前列腺癌的进展
DOI：
10.3390/ijms23126573
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发表时间：
2022-06-12
影响因子：
5.6
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Ma N;Liu H;Wu Y;Yao M;Zhang B
通过其特异性抑制剂瑞莫德林（Remodelin）抑制N -乙酰基转移酶10（NAT10）来抑制癌症已在多种人类癌症中得到证实。在此，我们报告了瑞莫德林对前列腺癌（PCa）细胞的抑制作用以及可能相关的机制。使用了前列腺癌细胞系VCaP、LNCaP、PC3和DU145。分别通过细胞增殖实验、集落形成实验、划痕实验和Transwell实验来检测细胞的体外增殖、迁移和侵袭能力。通过移植到裸鼠体内来分析体内肿瘤生长情况。瑞莫德林对NAT10的抑制不仅在体外抑制了前列腺癌细胞的生长、迁移和侵袭，而且也抑制了其体内肿瘤生长。通过EdU标记、DNA铺展、iPOND和ChIP - PCR实验评估了NAT10在DNA复制中的作用。瑞莫德林对NAT10的抑制减缓了DNA复制。在预复制复合物中检测到NAT10，并且它还能与DNA复制起点结合。此外，通过免疫共沉淀（Co - IP）分析了NAT10和CDC6之间的相互作用。通过免疫荧光染色和蛋白质印迹法（Western blotting）检测NAT10表达的变化。瑞莫德林显著降低了CDC6和雄激素受体（AR）的水平。在去势或非去势条件下，NAT10的表达均可改变，并且瑞莫德林仍然抑制体外诱导的去势抵抗性前列腺癌的生长。对癌症基因组图谱（TCGA）数据库的分析显示，前列腺癌中NAT10、CDC6和MCM7的过表达与格里森评分（Gleason score）和淋巴结转移相关。我们的数据表明，NAT10的抑制剂瑞莫德林在去势或非去势条件下均能有效抑制前列腺癌细胞的生长，可能是通过损害DNA复制来实现的。
Cancer suppression through the inhibition of N-acetyltransferase 10 (NAT10) by its specific inhibitor Remodelin has been demonstrated in a variety of human cancers. Here, we report the inhibitory effects of Remodelin on prostate cancer (PCa) cells and the possible associated mechanisms. The prostate cancer cell lines VCaP, LNCaP, PC3, and DU145 were used. The in vitro proliferation, migration, and invasion of cells were measured by a cell proliferation assay, colony formation, wound healing, and Transwell assays, respectively. In vivo tumor growth was analyzed by transplantation into nude mice. The inhibition of NAT10 by Remodelin not only suppressed growth, migration, and invasion in vitro, but also the in vivo cancer growth of prostate cancer cells. The involvement of NAT10 in DNA replication was assessed by EdU labeling, DNA spreading, iPOND, and ChIP-PCR assays. The inhibition of NAT10 by Remodelin slowed DNA replication. NAT10 was detected in the prereplication complex, and it could also bind to DNA replication origins. Furthermore, the interaction between NAT10 and CDC6 was analyzed by Co-IP. The altered expression of NAT10 was measured by immunofluorescence staining and Western blotting. Remodelin markedly reduced the levels of CDC6 and AR. The expression of NAT10 could be altered under either castration or noncastration conditions, and Remodelin still suppressed the growth of in vitro-induced castration-resistant prostate cancers. The analysis of a TCGA database revealed that the overexpression of NAT10, CDC6, and MCM7 in prostate cancers were correlated with the Gleason score and node metastasis. Our data demonstrated that Remodelin, an inhibitor of NAT10, effectively inhibits the growth of prostate cancer cells under either no castration or castration conditions, likely by impairing DNA replication.
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DOI：
10.1007/978-1-4939-1680-1_10
发表时间：
2015
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Dungrawala, Huzefa;Cortez, David
通讯作者：
Cortez, David
影响因子：
2.8
作者：
Mediwala, Sanjay N.;Sun, Huiying;Szafran, Adam T.;Hartig, Sean M.;Sonpavde, Guru;Hayes, Teresa G.;Thiagarajan, Perumal;Mancini, Michael A.;Marcelli, Marco
通讯作者：
Marcelli, Marco
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J
影响因子：
8.8
作者：
Karanika S;Karantanos T;Li L;Wang J;Park S;Yang G;Zuo X;Song JH;Maity SN;Manyam GC;Broom B;Aparicio AM;Gallick GE;Troncoso P;Corn PG;Navone N;Zhang W;Li S;Thompson TC
通讯作者：
Thompson TC
DOI：
10.1038/ncpuro1296
发表时间：
2009-02
期刊：
NATURE CLINICAL PRACTICE UROLOGY
影响因子：
--
作者：
Harris, William P.;Mostaghel, Elahe A.;Nelson, Peter S.;Montgomery, Bruce
通讯作者：
Montgomery, Bruce