RNF126-mediated ubiquitination of FSP1 affects its subcellular localization and ferroptosis
© 2024. The Author(s), under exclusive licence to Springer Nature Limited..
Medulloblastoma (MB) is a prevalent malignant brain tumor among children, which can be classified into four primary molecular subgroups. Group 3 MB (G3-MB) is known to be highly aggressive and associated with a poor prognosis, necessitating the development of novel and effective therapeutic interventions. Ferroptosis, a regulated form of cell death induced by lipid peroxidation, has been identified as a natural tumor suppression mechanism in various cancers. Nevertheless, the potential role of ferroptosis in the treatment of G3-MB remains unexplored. In this study, we demonstrate that RNF126 acts as an anti-ferroptotic gene by interacting with ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) and ubiquitinating FSP1 at the 4KR-2 sites. Additionally, the deletion of RNF126 reduces the subcellular localization of FSP1 in the plasma membrane, resulting in an increase in the CoQ/CoQH2 ratio in G3-MB. The RNF126-FSP1-CoQ10 pathway plays a pivotal role in suppressing phospholipid peroxidation and ferroptosis both in vivo and in vitro. Clinically, RNF126 exhibited elevated expression in G3-MB and its overexpression was significantly associated with reduced patient survival. Our findings indicate that RNF126 regulates G3-MB sensitivity to ferroptosis by ubiquitinating FSP1, which provides new evidence for the potential G3-MB therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Oncogene - (2024) vom: 21. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xie, Wanqun [VerfasserIn] |
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Date Revised 22.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1038/s41388-024-02949-x |
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| PPN (Katalog-ID): |
NLM370044339 |
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| 520 | |a Medulloblastoma (MB) is a prevalent malignant brain tumor among children, which can be classified into four primary molecular subgroups. Group 3 MB (G3-MB) is known to be highly aggressive and associated with a poor prognosis, necessitating the development of novel and effective therapeutic interventions. Ferroptosis, a regulated form of cell death induced by lipid peroxidation, has been identified as a natural tumor suppression mechanism in various cancers. Nevertheless, the potential role of ferroptosis in the treatment of G3-MB remains unexplored. In this study, we demonstrate that RNF126 acts as an anti-ferroptotic gene by interacting with ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) and ubiquitinating FSP1 at the 4KR-2 sites. Additionally, the deletion of RNF126 reduces the subcellular localization of FSP1 in the plasma membrane, resulting in an increase in the CoQ/CoQH2 ratio in G3-MB. The RNF126-FSP1-CoQ10 pathway plays a pivotal role in suppressing phospholipid peroxidation and ferroptosis both in vivo and in vitro. Clinically, RNF126 exhibited elevated expression in G3-MB and its overexpression was significantly associated with reduced patient survival. Our findings indicate that RNF126 regulates G3-MB sensitivity to ferroptosis by ubiquitinating FSP1, which provides new evidence for the potential G3-MB therapy | ||
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| 700 | 1 | |a Tian, Shuaiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Liangliang |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Zhuangzhuang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Baocheng |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jie |e verfasserin |4 aut | |
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