|
| Status |
Public on Jan 14, 2022 |
| Title |
RB1 loss promotes a noncanonical activator function of LSD1 and sensitizes castration-resistant prostate cancer to LSD1 inhibition [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Genomic loss of RB1 is a common alteration in castration-resistant prostate cancer (CRPC) and is associated with poor patient outcomes. RB1-loss is also a driver event that promotes the neuroendocrine transdifferentiation of prostate cancer (PCa). The loss of Rb protein disrupts the Rb-E2F repressor complex and thus hyperactivates E2F transcription activators. While the impact of RB1-loss on PCa progression and linage plasticity has been previously studied, the underline mechanisms remain unclear. Using an integrated cistromic and transcriptomic analysis, we have characterized Rb activities in multiple CRPC models by identifying Rb directly regulated genes and revealed that Rb has distinct binding sites and targets in TP53-mutated CRPC. Significantly, we show that RB1-loss promotes the noncanonical activator function of LSD1/KDM1A, which stabilizes chromatin binding of E2F1, and hence sensitizes CRPC tumor to the LSD1 inhibitor treatment. These results provide new molecular insights of Rb activity in PCa progression and suggest LSD1 as a potential therapeutic target in CRPC with RB1-loss.
|
| |
|
| Overall design |
C4-2-tet-shRB cells were treated with either vehicle or DHT (10nM, 24 hours) under different conditions of doxycycline induction (0, 3, or 30 days). For RNA-seq of GSK study, LNCaP cells were treated with/out 1μM GSK2879552 for 2 days, and C4-2-tet-shRB cells were treated with/out 10μM GSK2879552 for 24 hours under doxycycline condition or not. VCaP cells were transfected with siNTC or siRB. All RNA-seq samples contain replications.
|
| |
|
| Contributor(s) |
Han W, Liu M, Han D, Gao S, Cai C |
| Citation(s) |
34975152 |
| |
| Submission date |
Jun 08, 2021 |
| Last update date |
Jan 14, 2022 |
| Contact name |
Changmeng Cai |
| E-mail(s) |
changmeng.cai@umb.edu
|
| Organization name |
University of Massachusetts Boston
|
| Street address |
100 William T Morrissey Blvd
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02125 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL30173 |
NextSeq 2000 (Homo sapiens) |
|
| Samples (30)
|
|
| This SubSeries is part of SuperSeries: |
| GSE176404 |
RB1 loss promotes a noncanonical activator function of LSD1 and sensitizes castration-resistant prostate cancer to LSD1 inhibition |
|
| Relations |
| BioProject |
PRJNA736079 |
| SRA |
SRP323251 |
Less...
More...