CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma
Neuroblastoma (NB) is a devastating malignancy threatening children’s health, and amplification of MYCN is associated with treatment failure and a poor outcome. Here, we aimed to demonstrate the role of cell division cycle 27 (CDC27), an important core subunit of the anaphase-promoting complex, and...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.774458/full |
| _version_ | 1819278405751799808 |
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| author | Lin Qiu Rui Zhou Rui Zhou Ziyan Luo Jiangxue Wu Hua Jiang |
| author_facet | Lin Qiu Rui Zhou Rui Zhou Ziyan Luo Jiangxue Wu Hua Jiang |
| author_sort | Lin Qiu |
| collection | DOAJ |
| description | Neuroblastoma (NB) is a devastating malignancy threatening children’s health, and amplification of MYCN is associated with treatment failure and a poor outcome. Here, we aimed to demonstrate the role of cell division cycle 27 (CDC27), an important core subunit of the anaphase-promoting complex, and its clinical significance in NB patients. In functional assays, we illustrated that CDC27 promoted the cell growth, metastasis and sphere-formation ability of NB cells both in vitro and in vivo. To further understand the potential mechanism, SK-N-SH cells were transfected with CDC27 siRNA, and RNA-sequencing was performed. The results revealed that downregulation of CDC27 led to markedly reduced expression of ODC1, which is a well-established direct target of MYCN. Subsequently, we further illustrated that suppression of ODC1 significantly attenuated the promotion effect of CDC27 on the proliferation, metastasis, and sphere-formation ability of NB cells, hinting that CDC27 exerted its biological behavior in NB at least partly in an ODC1-dependent manner. In addition, CDC27 rendered cells more vulnerable to ferroptosis, while knockdown of ODC1 markedly reversed the pro-ferroptotic effect of CDC27. Collectively, our data is the first to report that the CDC27/ODC1 axis promotes tumorigenesis and acts as a positive regulator of ferroptosis in NB, highlighting that CDC27 may represent a novel therapeutic strategy and prognostic biomarker in neuroblastoma. |
| first_indexed | 2024-12-24T00:11:29Z |
| format | Article |
| id | doaj.art-67caab8393774c4d8eaf3999e2bc643c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-24T00:11:29Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-67caab8393774c4d8eaf3999e2bc643c2022-12-21T17:24:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.774458774458CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in NeuroblastomaLin Qiu0Rui Zhou1Rui Zhou2Ziyan Luo3Jiangxue Wu4Hua Jiang5Department of Hematology/Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of General Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, ChinaDepartment of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Hematology/Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Hematology/Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaNeuroblastoma (NB) is a devastating malignancy threatening children’s health, and amplification of MYCN is associated with treatment failure and a poor outcome. Here, we aimed to demonstrate the role of cell division cycle 27 (CDC27), an important core subunit of the anaphase-promoting complex, and its clinical significance in NB patients. In functional assays, we illustrated that CDC27 promoted the cell growth, metastasis and sphere-formation ability of NB cells both in vitro and in vivo. To further understand the potential mechanism, SK-N-SH cells were transfected with CDC27 siRNA, and RNA-sequencing was performed. The results revealed that downregulation of CDC27 led to markedly reduced expression of ODC1, which is a well-established direct target of MYCN. Subsequently, we further illustrated that suppression of ODC1 significantly attenuated the promotion effect of CDC27 on the proliferation, metastasis, and sphere-formation ability of NB cells, hinting that CDC27 exerted its biological behavior in NB at least partly in an ODC1-dependent manner. In addition, CDC27 rendered cells more vulnerable to ferroptosis, while knockdown of ODC1 markedly reversed the pro-ferroptotic effect of CDC27. Collectively, our data is the first to report that the CDC27/ODC1 axis promotes tumorigenesis and acts as a positive regulator of ferroptosis in NB, highlighting that CDC27 may represent a novel therapeutic strategy and prognostic biomarker in neuroblastoma.https://www.frontiersin.org/articles/10.3389/fonc.2022.774458/fullCDC27ODC1neuroblastomametastasisferroptosis |
| spellingShingle | Lin Qiu Rui Zhou Rui Zhou Ziyan Luo Jiangxue Wu Hua Jiang CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma Frontiers in Oncology CDC27 ODC1 neuroblastoma metastasis ferroptosis |
| title | CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma |
| title_full | CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma |
| title_fullStr | CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma |
| title_full_unstemmed | CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma |
| title_short | CDC27-ODC1 Axis Promotes Metastasis, Accelerates Ferroptosis and Predicts Poor Prognosis in Neuroblastoma |
| title_sort | cdc27 odc1 axis promotes metastasis accelerates ferroptosis and predicts poor prognosis in neuroblastoma |
| topic | CDC27 ODC1 neuroblastoma metastasis ferroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.774458/full |
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