NASP implication in the androgen receptor associated with castration resistance in prostate cancer
Abstract Uncovering the mechanisms underlying tumor malignancy is extremely important for cancer treatment and management. In this study, using a pairwise cell model, LNCaP and its castration-resistant derivative C42B, we analyze the function of enhanced NASP protein in castration resistance. The da...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02339-0 |
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| author | Yun Feng Jin Sun Xuan Kang Yining Wang Kai Liu Wenfei Wang Chen Wang Yabin Li Qian Zhao Kaile Li Fang-Lin Sun Jianfeng Chang |
| author_facet | Yun Feng Jin Sun Xuan Kang Yining Wang Kai Liu Wenfei Wang Chen Wang Yabin Li Qian Zhao Kaile Li Fang-Lin Sun Jianfeng Chang |
| author_sort | Yun Feng |
| collection | DOAJ |
| description | Abstract Uncovering the mechanisms underlying tumor malignancy is extremely important for cancer treatment and management. In this study, using a pairwise cell model, LNCaP and its castration-resistant derivative C42B, we analyze the function of enhanced NASP protein in castration resistance. The data show that the expression of androgen receptor-targeted genes was obviously affected by NASP knockdown in C42B cells, and nearly 20% of the differential genes were AR dependent. ATAC-seq analysis revealed that NASP knockdown in C42B cells comprehensively increased chromatin accessibility, and disorders at AR occupancy regions were more prominent. Castration-induced genes, especially androgen-independent AR target genes, were enriched in the downregulated gene group. Further analysis of high-order chromatin interactions revealed that NASP knockdown in C42B led to frequent changes in multiple layers, including the compartment A/B transition, TAD boundary distance and chromatin loop, and AR-binding regions especially underwent more extensive reconstruction. Finally, we found that the recovery of the histone H3 pool in C42B can actually recall H3 back to the previous regions with both H3 and AR loss induced by NASP knockdown, but AR rebinding to the corresponding sites is obviously inhibited and lagging. These data indicate that NASP plays a fundamental role in guarding proper and fine mechanisms of AR in prostate cancer promotion and malignancy. |
| format | Article |
| id | doaj-art-fb6eb226da054a248937fb725076aadd |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-fb6eb226da054a248937fb725076aadd2025-08-20T03:46:15ZengBMCCell Communication and Signaling1478-811X2025-07-0123111710.1186/s12964-025-02339-0NASP implication in the androgen receptor associated with castration resistance in prostate cancerYun Feng0Jin Sun1Xuan Kang2Yining Wang3Kai Liu4Wenfei Wang5Chen Wang6Yabin Li7Qian Zhao8Kaile Li9Fang-Lin Sun10Jianfeng Chang11Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityTeaching Laboratory Center, School of Medicine, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityResearch Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji UniversityAbstract Uncovering the mechanisms underlying tumor malignancy is extremely important for cancer treatment and management. In this study, using a pairwise cell model, LNCaP and its castration-resistant derivative C42B, we analyze the function of enhanced NASP protein in castration resistance. The data show that the expression of androgen receptor-targeted genes was obviously affected by NASP knockdown in C42B cells, and nearly 20% of the differential genes were AR dependent. ATAC-seq analysis revealed that NASP knockdown in C42B cells comprehensively increased chromatin accessibility, and disorders at AR occupancy regions were more prominent. Castration-induced genes, especially androgen-independent AR target genes, were enriched in the downregulated gene group. Further analysis of high-order chromatin interactions revealed that NASP knockdown in C42B led to frequent changes in multiple layers, including the compartment A/B transition, TAD boundary distance and chromatin loop, and AR-binding regions especially underwent more extensive reconstruction. Finally, we found that the recovery of the histone H3 pool in C42B can actually recall H3 back to the previous regions with both H3 and AR loss induced by NASP knockdown, but AR rebinding to the corresponding sites is obviously inhibited and lagging. These data indicate that NASP plays a fundamental role in guarding proper and fine mechanisms of AR in prostate cancer promotion and malignancy.https://doi.org/10.1186/s12964-025-02339-0NASPAndrogen receptorProstate cancerEMTHistone turnoverEpigenetic landscape |
| spellingShingle | Yun Feng Jin Sun Xuan Kang Yining Wang Kai Liu Wenfei Wang Chen Wang Yabin Li Qian Zhao Kaile Li Fang-Lin Sun Jianfeng Chang NASP implication in the androgen receptor associated with castration resistance in prostate cancer Cell Communication and Signaling NASP Androgen receptor Prostate cancer EMT Histone turnover Epigenetic landscape |
| title | NASP implication in the androgen receptor associated with castration resistance in prostate cancer |
| title_full | NASP implication in the androgen receptor associated with castration resistance in prostate cancer |
| title_fullStr | NASP implication in the androgen receptor associated with castration resistance in prostate cancer |
| title_full_unstemmed | NASP implication in the androgen receptor associated with castration resistance in prostate cancer |
| title_short | NASP implication in the androgen receptor associated with castration resistance in prostate cancer |
| title_sort | nasp implication in the androgen receptor associated with castration resistance in prostate cancer |
| topic | NASP Androgen receptor Prostate cancer EMT Histone turnover Epigenetic landscape |
| url | https://doi.org/10.1186/s12964-025-02339-0 |
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