Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication
Cancer suppression through the inhibition of <i>N</i>-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 mecha...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ningning Ma Haijing Liu Yaqian Wu Mengfei Yao Bo Zhang |
| author_facet | Ningning Ma Haijing Liu Yaqian Wu Mengfei Yao Bo Zhang |
| author_sort | Ningning Ma |
| collection | DOAJ |
| description | Cancer suppression through the inhibition of <i>N</i>-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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| language | English |
| last_indexed | 2024-03-09T23:35:25Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bf1ec934d21f48bfad5dd57b2b5d6ada2023-11-23T17:03:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312657310.3390/ijms23126573Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA ReplicationNingning Ma0Haijing Liu1Yaqian Wu2Mengfei Yao3Bo Zhang4Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaDepartment of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaDepartment of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaDepartment of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaDepartment of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, ChinaCancer suppression through the inhibition of <i>N</i>-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.https://www.mdpi.com/1422-0067/23/12/6573<i>N</i>-acetyltransferase 10DNA replicationprostate cancerCRPCprogression |
| spellingShingle | Ningning Ma Haijing Liu Yaqian Wu Mengfei Yao Bo Zhang Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication International Journal of Molecular Sciences <i>N</i>-acetyltransferase 10 DNA replication prostate cancer CRPC progression |
| title | Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication |
| title_full | Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication |
| title_fullStr | Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication |
| title_full_unstemmed | Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication |
| title_short | Inhibition of <i>N</i>-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication |
| title_sort | inhibition of i n i acetyltransferase 10 suppresses the progression of prostate cancer through regulation of dna replication |
| topic | <i>N</i>-acetyltransferase 10 DNA replication prostate cancer CRPC progression |
| url | https://www.mdpi.com/1422-0067/23/12/6573 |
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