TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation
Neuroblastoma, predominantly afflicting young individuals, is characterized as an embryonal tumor, with poor prognosis primarily attributed to chemoresistance. This study delved into the impact of tripartite motif (TRIM) 59, an E3 ligase, on neuroblastoma development and chemosensitivity through med...
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024020450 |
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| author | Yingbei Liu Na Jiang Weicheng Chen Wenbo Zhang Xiao Shen Bing Jia Gang Chen |
| author_facet | Yingbei Liu Na Jiang Weicheng Chen Wenbo Zhang Xiao Shen Bing Jia Gang Chen |
| author_sort | Yingbei Liu |
| collection | DOAJ |
| description | Neuroblastoma, predominantly afflicting young individuals, is characterized as an embryonal tumor, with poor prognosis primarily attributed to chemoresistance. This study delved into the impact of tripartite motif (TRIM) 59, an E3 ligase, on neuroblastoma development and chemosensitivity through mediating ferroptosis and the involvement of the tumor suppressor p53. Clinical samples were assessed for TRIM59 and p53 levels to explore their correlation with neuroblastoma differentiation. In neuroblastoma cells, modulation of TRIM59 expression, either through overexpression or knockdown, was coupled with doxorubicin hydrochloride (DOX) or ferrostatin-1 (Fer-1) therapy. In vivo assessments examined the influence of TRIM59 knockdown on neuroblastoma chemosensitivity to DOX. Co-immunoprecipitation and ubiquitination assays investigated the association between TRIM59 and p53. Proliferation was gauged with Cell Counting Kit-8, lipid reactive oxygen species (ROS) were assessed via flow cytometry, and protein levels were determined by Western blotting. TRIM59 expression was inversely correlated with neuroblastoma differentiation and positively linked to cell proliferation in response to DOX. Moreover, TRIM59 impeded lipid ROS generation and ferroptosis by directly interacting with p53, promoting its ubiquitination and degradation in DOX-exposed neuroblastoma cells. Fer-1 countered the impact of TRIM59 knockdown on neuroblastoma, while TRIM59 knockdown enhanced the therapeutic efficacy of DOX in xenograph mice. This study underscores TRIM59 as an oncogene in neuroblastoma, fostering growth and chemoresistance by suppressing ferroptosis through p53 ubiquitination and degradation. TRIM59 emerges as a potential strategy for neuroblastoma therapy. |
| first_indexed | 2024-03-07T21:53:34Z |
| format | Article |
| id | doaj.art-adeb22dbaf56419fbc14e1d471f64146 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-25T01:21:40Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj.art-adeb22dbaf56419fbc14e1d471f641462024-03-09T09:26:52ZengElsevierHeliyon2405-84402024-02-01104e26014TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradationYingbei Liu0Na Jiang1Weicheng Chen2Wenbo Zhang3Xiao Shen4Bing Jia5Gang Chen6Department of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaDepartment of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaDepartment of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaDepartment of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaDepartment of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaCorresponding author.; Department of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaCorresponding author.; Department of Cardiothoracic Surgery, Children's Hospital of Fudan University. No.399, Wanyuan Road, Minhang District, Shanghai, 201102, ChinaNeuroblastoma, predominantly afflicting young individuals, is characterized as an embryonal tumor, with poor prognosis primarily attributed to chemoresistance. This study delved into the impact of tripartite motif (TRIM) 59, an E3 ligase, on neuroblastoma development and chemosensitivity through mediating ferroptosis and the involvement of the tumor suppressor p53. Clinical samples were assessed for TRIM59 and p53 levels to explore their correlation with neuroblastoma differentiation. In neuroblastoma cells, modulation of TRIM59 expression, either through overexpression or knockdown, was coupled with doxorubicin hydrochloride (DOX) or ferrostatin-1 (Fer-1) therapy. In vivo assessments examined the influence of TRIM59 knockdown on neuroblastoma chemosensitivity to DOX. Co-immunoprecipitation and ubiquitination assays investigated the association between TRIM59 and p53. Proliferation was gauged with Cell Counting Kit-8, lipid reactive oxygen species (ROS) were assessed via flow cytometry, and protein levels were determined by Western blotting. TRIM59 expression was inversely correlated with neuroblastoma differentiation and positively linked to cell proliferation in response to DOX. Moreover, TRIM59 impeded lipid ROS generation and ferroptosis by directly interacting with p53, promoting its ubiquitination and degradation in DOX-exposed neuroblastoma cells. Fer-1 countered the impact of TRIM59 knockdown on neuroblastoma, while TRIM59 knockdown enhanced the therapeutic efficacy of DOX in xenograph mice. This study underscores TRIM59 as an oncogene in neuroblastoma, fostering growth and chemoresistance by suppressing ferroptosis through p53 ubiquitination and degradation. TRIM59 emerges as a potential strategy for neuroblastoma therapy.http://www.sciencedirect.com/science/article/pii/S2405844024020450NeuroblastomaTRIM59FerroptosisLipid ROSp53 |
| spellingShingle | Yingbei Liu Na Jiang Weicheng Chen Wenbo Zhang Xiao Shen Bing Jia Gang Chen TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation Heliyon Neuroblastoma TRIM59 Ferroptosis Lipid ROS p53 |
| title | TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation |
| title_full | TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation |
| title_fullStr | TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation |
| title_full_unstemmed | TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation |
| title_short | TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation |
| title_sort | trim59 mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation |
| topic | Neuroblastoma TRIM59 Ferroptosis Lipid ROS p53 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024020450 |
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