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| Status |
Public on Jan 01, 2024 |
| Title |
BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma drives human dilated cardiomyopathy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
By using a small molecule compound library targeting epigenetic enzymes we have identified BRD9 enzyme for eliminating CSCs. Genomic and proteomic studies revealed that BRD9/BAF complex regulates expression of stemness factors and chemoresistance by cooperating with TGFβ/Activin-SMAD2/3 signalling pathway. Chemical inhibition and genetic loss of function of BDR9 blocks the self-renewal of CSCs, reduces CSC invasiveness and resensitizes PDAC CSCs to conventional therapies. Analyses of chromatin architecture showed that BRD9 regulates the 3D chromatin looping between promoters and enhancers of stemness genes and EMT regulators in CSCs. BRD9 inhibition abrogated tumour formation in mice and eliminated CSCs in tumours from pancreatic cancer patients. Collectively, we uncovered BRD9 enzyme as an attractive therapeutic target for re-sensitizing and eliminating CSCs in pancreatic cancer patients.
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| Overall design |
By using a small molecule compound library targeting epigenetic enzymes we have identified BRD9 enzyme for eliminating CSCs. Genomic and proteomic studies revealed that BRD9/BAF complex regulates expression of stemness factors and chemoresistance by cooperating with TGFβ/Activin-SMAD2/3 signalling pathway. Chemical inhibition and genetic loss of function of BDR9 blocks the self-renewal of CSCs, reduces CSC invasiveness and resensitizes PDAC CSCs to conventional therapies. Analyses of chromatin architecture showed that BRD9 regulates the 3D chromatin looping between promoters and enhancers of stemness genes and EMT regulators in CSCs. BRD9 inhibition abrogated tumour formation in mice and eliminated CSCs in tumours from pancreatic cancer patients. Collectively, we uncovered BRD9 enzyme as an attractive therapeutic target for re-sensitizing and eliminating CSCs in pancreatic cancer patients.
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| Contributor(s) |
Feng Y, Cai L, Chang C, Liu F, Jiang L, Pauklin S |
| Citation(s) |
37739089 |
| |
| Submission date |
Jan 16, 2023 |
| Last update date |
Sep 05, 2024 |
| Contact name |
Lei Jiang |
| E-mail(s) |
altacount55@gmail.com
|
| Organization name |
Guangdong Provincial People's Hospital
|
| Street address |
No.106 Zhongshan 2nd Road
|
| City |
Guangzhou |
| ZIP/Postal code |
510000 |
| Country |
France |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA924277 |
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