| Autor: |
Zhenlong Shao, Shutong Liu, Wenshuang Sun, Xuefen Zhuang, Shusha Yin, Ji Cheng, Xiaohong Xia, Yuning Liao, Jinbao Liu, Hongbiao Huang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cellular & Molecular Biology Letters, Vol 29, Iss 1, Pp 1-20 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1689-1392 |
| DOI: |
10.1186/s11658-024-00665-8 |
| Popis: |
Abstract Background Sentrin/SUMO-specific protease 3 (SENP3) is essential to regulate protein stability and function in normal and cancer cells. Nevertheless, its role and action mechanisms in prostate cancer (PCa) remain elusive. Thus, clarification of SENP3’s involvement and the SUMOylation process in PCa is pivotal for discovering potential targets and understanding SUMOylation dynamics. Methods Cell viability, EdU staining, live cell imaging, and cell cycle assays were used to determine proliferation of PCa cells. Transwell and wound-healing assays were used to detect migration of PCa cells. The interaction between SENP3 and SIX1 was determined by co-immunoprecipitation, western blotting, and immunofluorescence assays. Xenograft models established on NOD-SCID mice were used to evaluate in vivo effects post SENP3 knockdown. Immunohistochemistry was performed to investigate the expression of SENP3 in PCa tissues. Results This study found that SENP3 is highly expressed in PCa cell lines and tissues from PCa patients. Overexpressed SENP3 is associated with metastatic malignancy in PCa. Various in vivo and in vitro experiments confirmed that SENP3 promotes the proliferation and migration of PCa. In addition, SENP3 interacts with the SD domain of SIX1 and mediates its deSUMOylation and protein stability. Lys154 (K154) is required for the SUMOylation of SIX1. More importantly, SENP3 promotes the malignancy of PCa through the regulation of SIX1. Conclusions We unravel the significant role of SENP3 in regulating protein stability of SIX1 and progression of PCa, which may deepen our understanding of the SUMOylation modification and provide a promising target for management of metastatic PCa. |
| Databáze: |
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| Externí odkaz: |
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