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| Status |
Public on Aug 09, 2024 |
| Title |
Cytoplasmic UHRF1 restrains MHC-I-mediated anti-tumor immune response [bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immunotherapy has revolutionized the landscape of cancer treatment. However, both primary and acquired resistance to immunotherapy, emerged during the co-evolution of cancer cells and the tumor microenvironment (TME), commonly restrain long-term tumor control. In exploring the oncogenic activity of Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), we unexpectedly discovered that this epigenetic regulator exhibits altered expression and aberrant cytosolic localization in cancerous tissues. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the TME, such as TGF-, enabling UHRF1 to bind MHC-I and promote its ubiquitination and degradation via the E3 activity of UHRF1. Down-regulation of MHC-I results in suppression of the antigen presentation pathway to establish a non-T cell-inflamed TME favoring tumor growth. Genetic deletion of UHRF1 synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumor memory response by evoking low-affinity T cells upon sustained UHRF1 inactivation. Our study unveils a novel function of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.
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| Overall design |
One million sgNT or sgUHRF1 LG1233-OVA cells were subcutaneously injected into female C57BL/6 mice. Tumor tissues were collected on day 27 for RNA-sequencing.
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| Contributor(s) |
Tan L, Yin T, Wang L, Mudgal P, Li Q, Wang X |
| Citation(s) |
39362877 |
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| Submission date |
Jul 23, 2024 |
| Last update date |
Oct 15, 2024 |
| Contact name |
Liuyang Wang |
| Organization name |
Duke University
|
| Street address |
213 Research Drive
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| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27710 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1139165 |
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