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| Status |
Public on Jun 24, 2019 |
| Title |
Gene expression profilings for prostate cancer cells after inhibition of PARP1 or PARP2 using pharmaceutical or siRNA-based approaches |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa) growth and progression. Understanding the factors influencing AR-mediated transcription provides new opportunities for therapeutic intervention. We have previously discovered that a genetic variant in one of the DNA repair genes, PARP2, is associated with aggressive PCa. Here, we show that a high expression level of PARP2 in PCa tumors is associated with high Gleason scores and biochemical recurrence using The Cancer Genome Atlas (TCGA) dataset. Functional studies reveal that PARP2 enhances AR-mediated gene expression through interacting with the pioneer factor FOXA1 and facilitating AR recruitment to the enhancer regions genome-wide in PCa cells. Selective targeting of PARP2, but not PARP1, by genetic or pharmacological means blocks interaction between PARP2 and FOXA1, which in turn attenuates AR-mediated transcription and inhibits AR-positive PCa growth.
SIGNIFICANCE: Current anti-androgens act through blocking ligand binding or inhibiting androgen synthesis. Selective targeting of PARP2 may provide a novel therapeutic approach for AR inhibition by disruption of FOXA1 function, which may be beneficial to patients, irrespective of their DNA repair defect status and, more importantly, when direct AR-targeted therapies fail.
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| |
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| Overall design |
Gene expression by RNA-Seq of LNCaP cells treated with PARP inhibitors or after PARP1/PARP2 gene knockdown, with biological duplicates.
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| Web link |
https://www.pnas.org/content/early/2019/07/01/1908547116.short?rss=1
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| |
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| Contributor(s) |
Gui B, Jia L |
| Citation(s) |
31266892 |
| |
| Submission date |
May 10, 2018 |
| Last update date |
Jul 09, 2019 |
| Contact name |
Li Jia |
| E-mail(s) |
[email protected]
|
| Organization name |
Brigham and Women's Hospital
|
| Department |
Surgery
|
| Lab |
Thorn 1529
|
| Street address |
20 Shattuck Street
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE114275 |
Selective Targeting of PARP2 Inhibits Androgen Receptor Signaling and Prostate Cancer Growth Through Disruption of FOXA1 Function |
|
| Relations |
| BioProject |
PRJNA471001 |
| SRA |
SRP145455 |
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