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| Status |
Public on Oct 03, 2024 |
| Title |
USP22 promotes the proliferation and inhibits Sorafenib-induced ferroptosis of hepatocellular carcinoma cells through its deubiquitinase activity [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Hepatocellular carcinoma (HCC) remains one of the most lethal cancers, characterized by poor prognosis and low life expectancy. Unfortunately, there are very few molecular therapeutic options available for advanced HCC. Sorafenib is a current standard first-line treatment for advanced HCC, but drug resistance significantly limits its therapeutic efficacy. In this study, we identified ubiquitin-specific protease 22 (USP22) as the key regulator of HCC development and Sorafenib resistance. Analysis of TCGA databases revealed that USP22 is highly expressed in HCC tissues and is closely associated with poor patient prognosis. Our data further indicated that USP22 promotes the proliferation of HCC cells via deubiquitinating and stabilizing cyclin-dependent kinase 11B (CDK11B). Additionally, USP22 acts as a novel inducer of Sorafenib resistance and suppresses Sorafenib-triggered ferroptosis in HCC cells. It reduces the transcription of the transferrin receptor (TFRC) by decreasing H2BK120ub occupancy at TFRC transcription start site (TSS) downstream region, thereby inhibiting ferroptosis upon Sorafenib treatment. Finally, animal experiments confirmed the role of USP22 in promoting HCC cell growth and Sorafenib resistance in vivo. Taken together, our findings suggest that USP22 represents a promising prognostic biomarker and therapeutic target for HCC patients, particularly those with Sorafenib resistance.
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| Overall design |
ChIP sequencing for H2BK120ub in Sorafenib-treated control and USP22 knockout HepG2 cells with Drosophila Schneider 2 cells (S2 cells) spike-in.
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| Contributor(s) |
Wang X |
| Citation missing |
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| |
| Submission date |
Oct 03, 2024 |
| Last update date |
Oct 04, 2024 |
| Contact name |
Bei Lan |
| E-mail(s) |
lanbei@tmu.edu.cn
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| Organization name |
Tianjin Medical University
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| Street address |
No22.Qixiangtai Rd.,Heping Dist,Tianjin P.R. China
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| City |
Tianjin |
| State/province |
天津Tianjin |
| ZIP/Postal code |
300070 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1168404 |
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