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Series GSE232554 Query DataSets for GSE232554
Status Public on Apr 22, 2024
Title FOXA2/AP-1 drives prostate cancer lineage plasticity [RNA-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary FOXA (Forkhead Box Protein A) family proteins function as pioneer transcription factors by loosening the compact chromatin structure and facilitating access for other transcription factors. The role of FOXA1 has been intensively studied in normal prostate epithelial cells and the adenocarcinoma subtype of prostate cancer (PCa) where it acts as a critical pioneer factor for the chromatin binding of androgen receptor (AR). Recent studies have indicated the emergence of FOXA2 as an adaptive response to AR signaling inhibition, particularly in prostate tumors that have undergone lineage reprogramming to a neuroendocrine PCa subtype. However, the molecular basis for this transition from FOXA1 to FOXA2 and its role in regulating the development of PCa lineage plasticity remains unclear. In this study, we show that FOXA2 binds to distinct chromatin regions in multiple AR-null PCa models with different molecular subtypes and that its binding is dependent on an epigenetic factor, LSD1. More importantly, we demonstrate that FOXA2 can function as a major pioneer factor of JUN and govern the chromatin binding of AP-1 complex in PCa exhibiting lineage plasticity. Mechanistically, differential reprogramming of JUN activates lineage-specific super-enhancers that may promote PCa progression by enhancing cell state transitions to multiple lineages. Overall, our study reveals a pivotal function of the LSD1-FOXA2 axis in rewiring AP-1 to induce differential transcriptional reprogramming required for PCa lineage plasticity.
Overall design Comparative gene expression profiling analysis was performed on RNA-seq data from PC3 cells under hormone-depleted conditions, which were transfected with siFOXA2, siJUN, and siNTC and treated with vehicle, LSD1 inhibitor ORY-1001 (10μM), and C12 (0.5μM) for 24 hours. We also conducted a similar analysis on RNA-seq data from NCI-H660 cells transfected with siFOXA2, siJUN, and siNTC. Furthermore, we carried out a comparative gene expression profiling analysis in LNCaP cells with stable FOXA2 overexpression (LN-FOXA2-OE) and negative control cells under hormone-depleted conditions.
Contributor(s) Wang Z, Cai C
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Submission date May 15, 2023
Last update date Apr 22, 2024
Contact name Zifeng Wang
Phone 6174709887
Organization name UMASS Boston
Department CPCT
Lab Changmeng Cai
Street address 100 Morrissey Blvd, ISC/4610
City Boston
State/province Massachusetts
ZIP/Postal code 02125
Country USA
Platforms (2)
GPL30172 NextSeq 2000 (Mus musculus)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (61)
GSM7350207 LNCaP_CTL_cells,vehicle, repeat 1
GSM7350208 LNCaP_CTL_cells,vehicle, repeat 2
GSM7350209 LNCaP_CTL_cells,vehicle, repeat 3
This SubSeries is part of SuperSeries:
GSE232555 FOXA2/AP-1 drives prostate cancer lineage plasticity
BioProject PRJNA972718

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE232554_DKO_siFOXA2_rawCount.txt.gz 404.1 Kb (ftp)(http) TXT
GSE232554_LN_FOXA2OE_DHT_rawCount.txt.gz 467.2 Kb (ftp)(http) TXT
GSE232554_LN_FOXA2OE_rawCount.txt.gz 466.3 Kb (ftp)(http) TXT
GSE232554_LN_FOXA2OEsiJUN_FOXA2K265R_rawCount.txt.gz 581.8 Kb (ftp)(http) TXT
GSE232554_NCIH660_LSD1i_rawCount.txt.gz 472.6 Kb (ftp)(http) TXT
GSE232554_NCIH660_siFOXA2_siJUN_rawCount.txt.gz 553.8 Kb (ftp)(http) TXT
GSE232554_PC3_LSD1i_rawCount.txt.gz 5.0 Mb (ftp)(http) TXT
GSE232554_PC3_siFOXA2_rawCount.txt.gz 450.1 Kb (ftp)(http) TXT
GSE232554_PC3_siJUN_rawCount.txt.gz 398.8 Kb (ftp)(http) TXT
GSE232554_PC3_siLSD1_rawCount.txt.gz 476.9 Kb (ftp)(http) TXT
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