SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10
Abstract Background Osteosarcoma (OS) is recognized as a prevalent primary bone malignancy, particularly affecting adolescents during their growth spurts. Despite its clinical significance, the underlying biological characteristics and associated prognostic factors remain incompletely understood. Th...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06248-1 |
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| author | Weilai Tong Xinsheng Xie Zhiguo Shu Jiangbo Nie Xianhe Yang Feng Yang Zhili Liu Jiaming Liu |
| author_facet | Weilai Tong Xinsheng Xie Zhiguo Shu Jiangbo Nie Xianhe Yang Feng Yang Zhili Liu Jiaming Liu |
| author_sort | Weilai Tong |
| collection | DOAJ |
| description | Abstract Background Osteosarcoma (OS) is recognized as a prevalent primary bone malignancy, particularly affecting adolescents during their growth spurts. Despite its clinical significance, the underlying biological characteristics and associated prognostic factors remain incompletely understood. The identification of novel molecular players involved in osteosarcoma progression could enhance our understanding of its pathogenesis and potentially inform patient management strategies. Methods In this study, we investigated the expression levels of Spindle and Centriole-Associated Protein 1 (SPICE1) in OS cells and tissues through quantitative analyses. We performed in vitro and in vivo experiments to evaluate the proliferation effects of SPICE1 on OS cells. Additionally, we explored the mechanistic interactions between SPICE1, Fatty Acid Synthase (FASN), and ubiquitin-specific peptidase 10 (USP10) through co-immunoprecipitation and mutation analyses, including the design of a peptide to inhibit the SPICE1-FASN interaction. Results Our findings revealed that SPICE1 is significantly overexpressed in OS samples. Furthermore, this high expression correlates with poor patient prognosis. The elevated levels of SPICE1 were found to promote OS cell proliferation by inhibiting the ubiquitination of FASN, consequently enhancing FASN protein stability. Additionally, SPICE1 was shown to facilitate the interaction between USP10 and FASN, promoting FASN deubiquitination, with specific amino acid interactions identified between USP10 and FASN that are necessary for this process. Conclusion This study elucidates the role of SPICE1 as a potential oncogene in OS, highlighting its contribution to tumor growth through the modulation of FASN stability. Importantly, our results suggest that targeting the SPICE1/USP10/FASN signaling axis could offer a novel therapeutic approach for treating OS. Future investigations should focus on the development of specific inhibitors that disrupt this pathway, ultimately leading to improved clinical outcomes for patients with OS. |
| format | Article |
| id | doaj-art-ee8c8632566e4bcba9084c15f15dbcda |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-ee8c8632566e4bcba9084c15f15dbcda2025-08-20T02:15:11ZengBMCJournal of Translational Medicine1479-58762025-02-0123111610.1186/s12967-025-06248-1SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10Weilai Tong0Xinsheng Xie1Zhiguo Shu2Jiangbo Nie3Xianhe Yang4Feng Yang5Zhili Liu6Jiaming Liu7Department of Orthopedic Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityJiangxi Provincial Key Laboratory of Spine and Spinal Cord DiseasesDepartment of Orthopedic Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopedic Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityMedical Innovation Center, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopedic Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopedic Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Orthopedic Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityAbstract Background Osteosarcoma (OS) is recognized as a prevalent primary bone malignancy, particularly affecting adolescents during their growth spurts. Despite its clinical significance, the underlying biological characteristics and associated prognostic factors remain incompletely understood. The identification of novel molecular players involved in osteosarcoma progression could enhance our understanding of its pathogenesis and potentially inform patient management strategies. Methods In this study, we investigated the expression levels of Spindle and Centriole-Associated Protein 1 (SPICE1) in OS cells and tissues through quantitative analyses. We performed in vitro and in vivo experiments to evaluate the proliferation effects of SPICE1 on OS cells. Additionally, we explored the mechanistic interactions between SPICE1, Fatty Acid Synthase (FASN), and ubiquitin-specific peptidase 10 (USP10) through co-immunoprecipitation and mutation analyses, including the design of a peptide to inhibit the SPICE1-FASN interaction. Results Our findings revealed that SPICE1 is significantly overexpressed in OS samples. Furthermore, this high expression correlates with poor patient prognosis. The elevated levels of SPICE1 were found to promote OS cell proliferation by inhibiting the ubiquitination of FASN, consequently enhancing FASN protein stability. Additionally, SPICE1 was shown to facilitate the interaction between USP10 and FASN, promoting FASN deubiquitination, with specific amino acid interactions identified between USP10 and FASN that are necessary for this process. Conclusion This study elucidates the role of SPICE1 as a potential oncogene in OS, highlighting its contribution to tumor growth through the modulation of FASN stability. Importantly, our results suggest that targeting the SPICE1/USP10/FASN signaling axis could offer a novel therapeutic approach for treating OS. Future investigations should focus on the development of specific inhibitors that disrupt this pathway, ultimately leading to improved clinical outcomes for patients with OS.https://doi.org/10.1186/s12967-025-06248-1OsteosarcomaSPICE1FASNUSP10Deubiquitination |
| spellingShingle | Weilai Tong Xinsheng Xie Zhiguo Shu Jiangbo Nie Xianhe Yang Feng Yang Zhili Liu Jiaming Liu SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10 Journal of Translational Medicine Osteosarcoma SPICE1 FASN USP10 Deubiquitination |
| title | SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10 |
| title_full | SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10 |
| title_fullStr | SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10 |
| title_full_unstemmed | SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10 |
| title_short | SPICE1 promotes osteosarcoma growth by enhancing the deubiquitination of FASN mediated by USP10 |
| title_sort | spice1 promotes osteosarcoma growth by enhancing the deubiquitination of fasn mediated by usp10 |
| topic | Osteosarcoma SPICE1 FASN USP10 Deubiquitination |
| url | https://doi.org/10.1186/s12967-025-06248-1 |
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