|
| Status |
Public on Mar 04, 2024 |
| Title |
KDM4 inhibition disrupts the core regulatory transcriptional circuitry in MYCN-driven neuroblastoma [Cut&Tag] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
A small set of interconnected lineage-specific transcription factors (TFs) form a core regulatory circuitry (CRC) that establishes and maintains cell identity and grants selective dependencies of distinct cancer types. However, effective therapies to targeting CRC TFs remain lacking. Here, we show that the best-in-class KDM4 inhibitor QC6352 has a potent anticancer activity in MYCN-driven high-risk neuroblastoma and significantly represses the CRC TFs including MYCN, HAND2, ASCL1, PHOX2B by disrupting the super-enhancers that dominate the expression of CRC TFs. Furthermore, we have developed a combination therapy by integrating QC6352 into cytotoxic chemotherapy, which leads to a complete response of MYCN amplified tumors and a better animal survival. This study reveals that targeting histone lysine demethylase 4 family may transform into a therapeutic strategy in clinic for cancers driven by CRC TFs.
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| |
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| Overall design |
Examination of chromatin accessibility, histone modification post QC6352 treatment in BE2C.
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| |
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| Contributor(s) |
Jie F, Hongjian J, Jun Y |
| Citation(s) |
38508144 |
| |
| Submission date |
Jan 08, 2021 |
| Last update date |
Jun 03, 2024 |
| Contact name |
Hongjian Jin |
| E-mail(s) |
hongjian.jin@STJUDE.ORG
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Center for Applied Bioinformatics
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38015 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE164456 |
Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma |
|
| Relations |
| BioProject |
PRJNA690791 |
| SRA |
SRP300908 |
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