Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation
© 2024. The Author(s)..
BACKGROUND: Ubiquitination is a critical post-translational modification which can be reversed with an enzyme family known as deubiquitinating enzymes (DUBs). It has been reported that dysregulation of deubiquitination leads to carcinogenesis. As a member of the DUBs family, proteasome 26 S subunit non-ATPase 7 (PSMD7) serves as an underlying tumour-promoting factor in multiple cancers. However, the clinical significance and biological functions of PSMD7 in pancreatic cancer (PC) remain unclear.
RESULTS: In this study, we first reported frequent overexpression of PSMD7 in PC tissues, and high levels of PSMD7 were markedly linked to shorter survival and a malignant phenotype in PC patients. An array of in vitro and in vivo gain/loss-of-function tests revealed that PSMD7 facilitates the progression of PC cells. Additionally, we found that PSMD7 promotes PC cell progression by activating the Notch homolog 1 (Notch1) signalling. Interestingly, in PC cells, the inhibitory effect of PSMD7 knockdown on cellular processes was comparable to that observed upon Notch1 knockdown. Mechanistically, PSMD7 deubiquitinated and stabilised sex determining region Y (SRY)-box 2 (SOX2), a key mediator of Notch1 signalling. The stabilisation of SOX2, mediated by PSMD7, dramatically increased SOX2 protein levels, subsequently activating the Notch1 pathway. Finally, restoration of SOX2 expression abrogated the PSMD7-silenced antitumour effect.
CONCLUSIONS: Taken together, our work identifies and validates PSMD7 as a promoter of PC progression through augmentation of the Notch1 signalling pathway mediated by SOX2. This finding suggests that PSMD7 holds promise as a potential therapeutic target for the management of this refractory disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Cell & bioscience - 14(2024), 1 vom: 17. März, Seite 35 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Luo, Chen [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 20.03.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s13578-024-01213-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369841646 |
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| 245 | 1 | 0 | |a Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Ubiquitination is a critical post-translational modification which can be reversed with an enzyme family known as deubiquitinating enzymes (DUBs). It has been reported that dysregulation of deubiquitination leads to carcinogenesis. As a member of the DUBs family, proteasome 26 S subunit non-ATPase 7 (PSMD7) serves as an underlying tumour-promoting factor in multiple cancers. However, the clinical significance and biological functions of PSMD7 in pancreatic cancer (PC) remain unclear | ||
| 520 | |a RESULTS: In this study, we first reported frequent overexpression of PSMD7 in PC tissues, and high levels of PSMD7 were markedly linked to shorter survival and a malignant phenotype in PC patients. An array of in vitro and in vivo gain/loss-of-function tests revealed that PSMD7 facilitates the progression of PC cells. Additionally, we found that PSMD7 promotes PC cell progression by activating the Notch homolog 1 (Notch1) signalling. Interestingly, in PC cells, the inhibitory effect of PSMD7 knockdown on cellular processes was comparable to that observed upon Notch1 knockdown. Mechanistically, PSMD7 deubiquitinated and stabilised sex determining region Y (SRY)-box 2 (SOX2), a key mediator of Notch1 signalling. The stabilisation of SOX2, mediated by PSMD7, dramatically increased SOX2 protein levels, subsequently activating the Notch1 pathway. Finally, restoration of SOX2 expression abrogated the PSMD7-silenced antitumour effect | ||
| 520 | |a CONCLUSIONS: Taken together, our work identifies and validates PSMD7 as a promoter of PC progression through augmentation of the Notch1 signalling pathway mediated by SOX2. This finding suggests that PSMD7 holds promise as a potential therapeutic target for the management of this refractory disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Notch1 | |
| 650 | 4 | |a PSMD7 | |
| 650 | 4 | |a Pancreatic cancer | |
| 650 | 4 | |a Proliferation | |
| 650 | 4 | |a SOX2 | |
| 700 | 1 | |a Yu, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jinfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Leifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Xingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zitao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Rongfa |e verfasserin |4 aut | |
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