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| Status |
Public on Jun 20, 2024 |
| Title |
EZH2 protects mucosal melanoma from ferroptosis via the KLF14-SLC7A11 signaling pathway (ChIP-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Background: Mucosal melanoma (MM) is epidemiologically, biologically, and molecularly distinct from cutaneous melanoma. Current treatment strategies have failed to significantly improve the prognosis for MM patients. This study aims to identify therapeutic targets and develop combination strategies by investigating the mechanisms underlying the tumorigenesis and progression of MM. Methods: We analyzed the copy number amplification of EZH2 in 547 melanoma patients and investigated its correlation with clinical prognosis. Utilizing cell lines, organoids, and patient-derived xenograft models, we assessed the impact of EZH2 on cell proliferation and sensitivity to ferroptosis. Further, we explored the mechanisms of ferroptosis resistance associated with EZH2 by conducting RNA sequencing and chromatin immunoprecipitation sequencing. Results: EZH2 copy number amplification was closely associated with malignant phenotype and poor prognosis in MM patients. EZH2 was essential for MM cell proliferation in vitro and in vivo. Moreover, genetic perturbation of EZH2 rendered MM cells sensitized to ferroptosis. Combination treatment of EZH2 inhibitor with ferroptosis inducer significantly inhibited the growth of MM. Mechanistically, EZH2 inhibited the expression of KLF14, which binds to the promoter of SLC7A11 to repress its transcription. Loss of EZH2 therefore reduced the expression of SLC7A11, leading to reduced intracellular SLC7A11-dependent glutathione synthesis to promote ferroptosis. Conclusion: Our findings not only establish EZH2 as a biomarker for MM prognosis, but also highlight the EZH2-KLF14-SLC7A11 axis as a potential target for MM treatment.
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| Overall design |
The submission includes samples from chromatin immunoprecipitation sequencing (ChIP-seq) experiments conducted on HMVII cells, a mucosal melanoma cell line. The primary objective of these experiments is to investigate the binding sites and genomic regions associated with EZH2, a key regulator in melanoma progression.
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| Contributor(s) |
Du H, Hou L, Yu H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jun 13, 2024 |
| Last update date |
Jun 21, 2024 |
| Contact name |
Haizhen Du |
| E-mail(s) |
[email protected]
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| Phone |
17839914360
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| Organization name |
Peking University Cancer Hospital and Institute
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| Street address |
No.52 Fucheng Road, Haidian District
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| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100142 |
| 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 |
PRJNA1123693 |
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