OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis
© 2023 The Authors..
O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
iScience - 26(2023), 11 vom: 17. Nov., Seite 108148 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Zhou [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer |
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| Anmerkungen: |
Date Revised 03.11.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2023.108148 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364075015 |
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| 520 | |a © 2023 The Authors. | ||
| 520 | |a O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Functional aspects of cell biology | |
| 650 | 4 | |a In vitro toxicology | |
| 650 | 4 | |a Molecular biology experimental approach | |
| 650 | 4 | |a Molecular network | |
| 700 | 1 | |a Wei, Xiyi |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Chengjian |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Xiaohan |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yichun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jingwan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Pengcheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Kejie |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Ninghong |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Chao |e verfasserin |4 aut | |
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