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| Status |
Public on Jan 09, 2024 |
| Title |
USP10-mediated MOF (KAT8) stabilization accelerates the malignant progression of esophageal squamous cell carcinoma via epigenetically activating of ANXA2/Wnt signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dysregulation of MOF (MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not enzyme inactive mutant (MOF E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and protects MOF from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription, which subsequently activates Wnt/ β-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.
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| Overall design |
To identify downstream targets mediating the oncogenic effect of MOF on ESCC progression, RNA-seq analysis was performed in Eca-109 cells respectively transfected with siRNAs against MOF (si-MOF#1 or si-MOF#2) or Negative control (si-NC). The amounts and integrity of total exacted RNA were analyzed using Bioanalyzer 2100 system (Agilent Technologies, CA, USA). Library preparation, sequencing and bioinformatic analysis were conducted at Novogene (Beijing, China).
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| Contributor(s) |
Zhao X, Sun H, Li P, Yang L |
| Citation(s) |
38317006 |
| |
| Submission date |
Aug 17, 2023 |
| Last update date |
Apr 10, 2024 |
| Contact name |
Peichao Li |
| E-mail(s) |
[email protected]
|
| Phone |
13705454987
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| Organization name |
Shandong University
|
| Department |
thoracic surgery department
|
| Lab |
Key Laboratory of Thoracic Oncology
|
| Street address |
The Second Hospital of Shandong University
|
| City |
Jinan |
| State/province |
Shangdong |
| ZIP/Postal code |
250012 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA1006336 |
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