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Series GSE134682 Query DataSets for GSE134682
Status Public on Jul 12, 2022
Title Pathologically stabilized GLI3 promotes androgen-independent growth of SPOP mutant prostate cancer cells through reactivation of an AR signaling axis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Although androgen deprivation therapy triggers a rapid response in men with metastatic prostate cancer, most patients eventually progress to lethal castration resistant prostate cancer (CRPC) characterized by androgen receptor (AR)-dependent tumor growth despite castrate levels of circulating androgens. Current treatment options for CRPC remain limited and non-curative, rendering improved outcomes dependent on deeper mechanistic insight and new therapeutic targets. In this RNA sequencing study we profiled the transcriptomes of SPOP WT and mutant LNCaP cells before and after androgen deprivation by RNA-sequencing. Using standard criteria (minimum 2-fold change), we identified 981 genes that were differentially expressed in SPOP mutant vs SPOP WT LNCaP cells grown in the absence of androgens . Strikingly, a significant fraction (595 or ~60%) of these genes overlapped with genes (3510 in number) differentially expressed as a function of androgen in WT LNCaP cells, indicating partial restoration of AR signaling in SPOP mutant cells following androgen withdrawal. To determine the contribution of GLI3 to this process, we performed RNA-sequencing following GLI3 knockdown in androgen-deprived SPOP mutant LNCaP cells. Among the 595 androgen-responsive genes in LNCaP cells whose hormone-independent expression is regulated by SPOP 187 (or ~31%) are also regulated by GLI3, thus revealing a prominent role for GLI3 in restoration of AR signaling in SPOP mutant cells following androgen withdrawal. Enrichment analysis using Gene Ontology Biological Processes revealed these 187 GLI3-regulated genes to be prominently linked with “chromosome segregation”, “DNA replication”, “transcriptional regulation of in G1/S transition”, “regulation of mitotic cell cycle”, and “chromatin silencing” among others, suggesting possible molecular genetic bases for androgen independent growth of SPOP mutant cells. Taken together, these findings indicate that SPOP mutant prostate cancer cells acquire robust androgen-independent growth through reestablishment of an AR signaling axis that involves functional crosstalk with the SHH/GLI3 pathway.
Overall design SPOP WT and SPOP mutant LNCaP cells that were transduced either with or without GLI3-specific shRNA-expressing lentivirus were grown in androgen replete or androgen deprived media. Total RNA was harvested and subjected to RNA sequencing.
Contributor(s) Burleson M, Boyer TG, Sun L, Zou Y, Chen Y
Citation(s) 34610962
Submission date Jul 22, 2019
Last update date Jul 14, 2022
Contact name YI ZOU
Organization name UTHSA-GCCRI
Street address 8403 Floyd Curl Drive
State/province TX
ZIP/Postal code 78229
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (18)
GSM3963308 SPOP WT +DHT repeat 1
GSM3963309 SPOP WT +DHT repeat 2
GSM3963310 SPOP WT -DHT repeat 1
BioProject PRJNA556036
SRA SRP215966

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Supplementary file Size Download File type/resource
GSE134682_RAW.tar 1.7 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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