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| Status |
Public on Jun 24, 2024 |
| Title |
Cut&Run SU-DIPG13 cells treated Sulfopin/Vorinostat/Sulfopin+Vorinostat or DMSO |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Diffuse midline gliomas (DMG) are aggressive pediatric tumors of the central nervous system that are highly resistant to treatments and are inevitably fatal. Lysine to methionine substitution of residue 27 on histone H3 (H3-K27M) is a driver mutation in DMGs, reshaping the epigenetic landscape of these cells to promote tumorigenesis. H3-K27M gliomas are characterized by deregulation of histone acetylation and methylation pathways, as well as the oncogenic MYC pathway. In search of effective treatment, we examined the therapeutic potential of dual targeting of histone deacetylases (HDACs) and MYC in these tumors. Treatment of H3-K27M patient-derived cells with Sulfopin, an inhibitor shown to block MYC-driven tumors in vivo, in combination with the HDAC inhibitor Vorinostat, resulted in substantial decrease in cell viability. Moreover, transcriptome and epigenome profiling revealed synergistic effect of this drug combination in downregulation of prominent oncogenic pathways such as mTOR. Finally, in vivo studies of patient-derived orthotopic xenograft models showed significant tumor size reduction in mice treated with the drug combination. These results highlight the combined treatment of Sulfopin and Vorinostat as a promising therapeutic approach for these aggressive tumors.
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| Overall design |
Cut and Run analysis performed on SU-DIPG 13 cells treated with Sulfopin/Vorinostat/Sulfopin+Vorinostat or DMSO, using the following primary antibodies: anti-histone H3K27me3 and anti-histone H3K27ac. Secondary antibody anti-rabbit HRP was used as a negative control.
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| Contributor(s) |
Algranati D, Dassa B, Shema E |
| Citation(s) |
39093942 |
| |
| Submission date |
Dec 22, 2022 |
| Last update date |
Aug 23, 2024 |
| Contact name |
Danielle Algranati |
| E-mail(s) |
Danielle.algranati@weizmann.ac.il
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| Organization name |
Weizmann Institute of Science
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| Department |
Department of Immunology & Regenerative Biology
|
| Lab |
Efrat Shema
|
| Street address |
234 Herzl Street
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| City |
Rehovot |
| ZIP/Postal code |
7610001 |
| Country |
Israel |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (9)
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| GSM6890291 |
Cut& Run on SU-DIPG13 treated with DMSO using H3K27ac ab |
| GSM6890292 |
Cut& Run on SU-DIPG13 treated with DMSO using H3K27me3 ab |
| GSM6890293 |
Cut& Run on SU-DIPG13 treated with Sulfopin using H3K27ac ab |
| GSM6890294 |
Cut& Run on SU-DIPG13 treated with Sulfopin using H3K27me3 ab |
| GSM6890295 |
Cut& Run on SU-DIPG13 treated with Vorinostat using H3K27ac ab |
| GSM6890296 |
Cut& Run on SU-DIPG13 treated with Vorinostat using H3K27me3 ab |
| GSM6890297 |
Cut& Run on SU-DIPG13 treated with Sulfopin+Vorinostat using H3K27ac ab |
| GSM6890298 |
Cut& Run on SU-DIPG13 treated with Sulfopin+Vorinostat using H3K27me3 ab |
| GSM6890299 |
Cut& Run on SU-DIPG13 using HRP ab |
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| This SubSeries is part of SuperSeries: |
| GSE221614 |
Cut&Run and MARS-seq on SU-DIPG13 cells treated Sulfopin/Vorinostat/Sulfopin+Vorinostat or DMSO |
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| Relations |
| BioProject |
PRJNA915081 |
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