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Series GSE176403 Query DataSets for GSE176403
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)
GSM5364054 C4-2-tet-shRB-Veh_rep1
GSM5364055 C4-2-tet-shRB-Veh_rep2
GSM5364056 C4-2-tet-shRB-DHT_rep1
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

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Supplementary file Size Download File type/resource
GSE176403_C42shRB_Dox_DHT_count_table.txt.gz 913.0 Kb (ftp)(http) TXT
GSE176403_C42shRB_Dox_GSK_count_table.txt.gz 840.2 Kb (ftp)(http) TXT
GSE176403_LNCaP_samples_count_table.txt.gz 611.0 Kb (ftp)(http) TXT
GSE176403_VCaP_samples_count_table.txt.gz 680.1 Kb (ftp)(http) TXT
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