c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy
Abstract Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. Differentiation status in neuroblastoma strongly affects the clinical outcome, thus, enforcement of differentiation becomes a treatment strategy for this disease. However, the molecular mec...
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2025-03-01
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| Online Access: | https://doi.org/10.1186/s13062-025-00630-1 |
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| author | Yunyun Wang Jingjing Huang Zhenhua Song Shuo Zhang Haojie Guo Qi Leng Na Fang Shaoping Ji Jian Yang |
| author_facet | Yunyun Wang Jingjing Huang Zhenhua Song Shuo Zhang Haojie Guo Qi Leng Na Fang Shaoping Ji Jian Yang |
| author_sort | Yunyun Wang |
| collection | DOAJ |
| description | Abstract Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. Differentiation status in neuroblastoma strongly affects the clinical outcome, thus, enforcement of differentiation becomes a treatment strategy for this disease. However, the molecular mechanisms that control neuroblastoma differentiation are poorly understood. As an extensively studied protein of the activator protein-1 (AP-1) complex, c-Jun is involved in numerous cell regulations such as proliferation, survival and differentiation. In the current study, we demonstrated that c-Jun expression was upregulated by retinoic acid (RA) and flow cytometry assay indicated c-Jun overexpression arrested cell cycle to G1 phase, which, in turn, promoted the initiation of neuroblastoma cell differentiation. Co-immunoprecipitation (co-IP) assay showed that c-Jun competitively interacted with CDC16, a key subunit in anaphase-promoting complex (APC), resulting in reduced APC formation and inhibition of cell cycle progression. Furthermore, EdU proliferation assay and transwell experiment showed that c-Jun overexpression inhibited neuroblastoma cell proliferation and migration via interacting and sequestering CDC16. These findings identify c-Jun as a key regulator of neuroblastoma cell cycle and differentiation and may represent a promising therapeutic target to induce neuroblastoma differentiation via the interaction between c-Jun and CDC16. |
| format | Article |
| id | doaj-art-325e7aab91094f67a3cc85d7c412bf08 |
| institution | Kabale University |
| issn | 1745-6150 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| spelling | doaj-art-325e7aab91094f67a3cc85d7c412bf082025-08-20T03:41:12ZengBMCBiology Direct1745-61502025-03-0120111710.1186/s13062-025-00630-1c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancyYunyun Wang0Jingjing Huang1Zhenhua Song2Shuo Zhang3Haojie Guo4Qi Leng5Na Fang6Shaoping Ji7Jian Yang8Department of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityDepartment of Biochemistry and Molecular Biology, Cell Signal Transduction Laboratory, School of Basic Medical Science, Henan UniversityCollege of Pharmacy and Nutrition, University of SaskatchewanAbstract Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. Differentiation status in neuroblastoma strongly affects the clinical outcome, thus, enforcement of differentiation becomes a treatment strategy for this disease. However, the molecular mechanisms that control neuroblastoma differentiation are poorly understood. As an extensively studied protein of the activator protein-1 (AP-1) complex, c-Jun is involved in numerous cell regulations such as proliferation, survival and differentiation. In the current study, we demonstrated that c-Jun expression was upregulated by retinoic acid (RA) and flow cytometry assay indicated c-Jun overexpression arrested cell cycle to G1 phase, which, in turn, promoted the initiation of neuroblastoma cell differentiation. Co-immunoprecipitation (co-IP) assay showed that c-Jun competitively interacted with CDC16, a key subunit in anaphase-promoting complex (APC), resulting in reduced APC formation and inhibition of cell cycle progression. Furthermore, EdU proliferation assay and transwell experiment showed that c-Jun overexpression inhibited neuroblastoma cell proliferation and migration via interacting and sequestering CDC16. These findings identify c-Jun as a key regulator of neuroblastoma cell cycle and differentiation and may represent a promising therapeutic target to induce neuroblastoma differentiation via the interaction between c-Jun and CDC16.https://doi.org/10.1186/s13062-025-00630-1c-JunCDC16Anaphase-promoting complexCell differentiationNeuroblastoma |
| spellingShingle | Yunyun Wang Jingjing Huang Zhenhua Song Shuo Zhang Haojie Guo Qi Leng Na Fang Shaoping Ji Jian Yang c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy Biology Direct c-Jun CDC16 Anaphase-promoting complex Cell differentiation Neuroblastoma |
| title | c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy |
| title_full | c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy |
| title_fullStr | c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy |
| title_full_unstemmed | c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy |
| title_short | c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy |
| title_sort | c jun promotes neuroblastoma cell differentiation by inhibiting apc formation via cdc16 and reduces neuroblastoma malignancy |
| topic | c-Jun CDC16 Anaphase-promoting complex Cell differentiation Neuroblastoma |
| url | https://doi.org/10.1186/s13062-025-00630-1 |
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