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| 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
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| 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.
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| 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.
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| Contributor(s) |
Wang Z, Cai C |
| Citation(s) |
38851846 |
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| Submission date |
May 15, 2023 |
| Last update date |
Jun 28, 2024 |
| Contact name |
Zifeng Wang |
| E-mail(s) |
[email protected]
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| Phone |
6174709887
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| Organization name |
UMASS Boston
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| Department |
CPCT
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| Lab |
Changmeng Cai
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| Street address |
100 Morrissey Blvd, ISC/4610
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02125 |
| Country |
USA |
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| Platforms (2) |
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| Samples (61)
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| GSM7350210 |
LNCaP_FOXA2OE, vehicle, repeat 1 |
| GSM7350211 |
LNCaP_FOXA2OE, vehicle, repeat 2 |
| GSM7350212 |
LNCaP_FOXA2OE, vehicle, repeat 3 |
| GSM7350213 |
LNCaP_CTL_cells, DHT 10nM repeat 1 |
| GSM7350214 |
LNCaP_CTL_cells, DHT 10nM repeat 2 |
| GSM7350215 |
LNCaP_CTL_cells, DHT 10nM repeat 3 |
| GSM7350216 |
LNCaP_FOXA2OE_cells, DHT 10nM repeat 1 |
| GSM7350217 |
LNCaP_FOXA2OE_cells, DHT 10nM repeat 2 |
| GSM7350218 |
LNCaP_FOXA2OE_cells, DHT 10nM repeat 3 |
| GSM7350219 |
NCI-H660 cells, siFOXA2, repeat 1 |
| GSM7350220 |
NCI-H660 cells, siFOXA2, repeat 2 |
| GSM7350221 |
NCI-H660 cells, siFOXA2, repeat 3 |
| GSM7350222 |
NCI-H660 cells, siJUN, repeat 1 |
| GSM7350223 |
NCI-H660 cells, siJUN, repeat 2 |
| GSM7350224 |
NCI-H660 cells, siJUN, repeat 3 |
| GSM7350225 |
NCI-H660 cells, siNC, repeat 1 |
| GSM7350226 |
NCI-H660 cells, siNC, repeat 2 |
| GSM7350227 |
NCI-H660 cells, siNC, repeat 3 |
| GSM7350228 |
PC3 cells, C12, repeat 1 |
| GSM7350229 |
PC3 cells, C12, repeat 2 |
| GSM7350230 |
PC3 cells, C12, repeat 3 |
| GSM7350231 |
PC3 cells, ORY-1001, repeat 1 |
| GSM7350232 |
PC3 cells, ORY-1001, repeat 2 |
| GSM7350233 |
PC3 cells, ORY-1001, repeat 3 |
| GSM7350234 |
PC3 cells, vehicle, repeat 1 |
| GSM7350235 |
PC3 cells, vehicle, repeat 2 |
| GSM7350236 |
PC3 cells, vehicle, repeat 3 |
| GSM7350237 |
PC3 cells, siJUN, repeat 1 |
| GSM7350238 |
PC3 cells, siJUN, repeat 2 |
| GSM7350239 |
PC3 cells, siNC, repeat 1 |
| GSM7350240 |
PC3 cells, siNC, repeat 2 |
| GSM7350241 |
PC3 cells, siFOXA2, repeat 1 |
| GSM7350242 |
PC3 cells, siFOXA2, repeat 2 |
| GSM7350243 |
PC3 cells, siFOXA2, repeat 3 |
| GSM7350244 |
PC3 cells, siNTC, repeat 1 |
| GSM7350245 |
PC3 cells, siNTC, repeat 2 |
| GSM7350246 |
PC3 cells, siNTC, repeat 3 |
| GSM8015489 |
LNCaP_FOXA2K265R, siNC, repeat 1 |
| GSM8015490 |
LNCaP_FOXA2K265R, siNC, repeat 2 |
| GSM8015491 |
LNCaP_FOXA2K265R, siNC, repeat 3 |
| GSM8015492 |
LNCaP_FOXA2OE, siJUN, repeat 1 |
| GSM8015493 |
LNCaP_FOXA2OE, siJUN, repeat 2 |
| GSM8015494 |
LNCaP_FOXA2OE, siJUN, repeat 3 |
| GSM8015495 |
LNCaP_FOXA2OE, siNC, repeat 1 |
| GSM8015496 |
LNCaP_FOXA2OE, siNC, repeat 2 |
| GSM8015497 |
LNCaP_FOXA2OE, siNC, repeat 3 |
| GSM8015498 |
PC3 cells, siLSD1, repeat 1 |
| GSM8015499 |
PC3 cells, siLSD1, repeat 2 |
| GSM8015500 |
PC3 cells, siLSD1, repeat 3 |
| GSM8015501 |
PC3 cells, siNTC, repeat 1 set2 |
| GSM8015502 |
PC3 cells, siNTC, repeat 2 set2 |
| GSM8015503 |
PC3 cells, siNTC, repeat 3 set2 |
| GSM8015504 |
DKO cells, siFOXA2, repeat 1 |
| GSM8015505 |
DKO cells, siFOXA2, repeat 2 |
| GSM8015506 |
DKO cells, siFOXA2, repeat 3 |
| GSM8015507 |
DKO cells, siNC, repeat 1 |
| GSM8015508 |
DKO cells, siNC, repeat 2 |
| GSM8015509 |
DKO cells, siNC, repeat 3 |
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| This SubSeries is part of SuperSeries: |
| GSE232555 |
FOXA2/AP-1 drives prostate cancer lineage plasticity |
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| Relations |
| BioProject |
PRJNA972718 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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