{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310685/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310685"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Minimal-length CAG repeats in AR define a hyperactive AR-LSD1 axis driving metabolic reprogramming in prostate cancer [ChIP-Seq]","description":"The polymorphic CAG trinucleotide repeat in the androgen receptor (AR) gene encodes a variable-length N-terminal polyglutamine (polyQ) tract that modulates AR transcriptional activity, with shorter tracts generally enhancing AR activity. While the majority of men harbor CAG repeats longer than 17, a small subset carry minimal-length CAG repeats (≤17) in AR. These alleles are primarily found in men of African ancestry (AA), accounting for over 10% of the population, and may significantly contribute to the increased prostate cancer (PCa) risk and worse clinical outcomes observed in AA men. However, how this distinct pattern of polymorphism influences AR-chromatin interaction, metabolic reprogramming, and therapeutic response remains unclear. Here, we established isogenic PCa cell lines harboring AR with a minimal length of CAG repeats that encode an ultrashort polyQ track and found that this AR variant exhibits resistance to AR-targeted therapy with markedly enhanced protein stability, expanded chromatin binding, and a reprogrammed transcriptional profile. Notably, the ultrashort polyQ AR also reshaped global FOXA1 occupancy and upregulated genes involved in fatty acid metabolism, lipid synthesis, and anaerobic glycolysis. Moreover, we identified a markedly increased AR-LSD1 interaction and showed that LSD1 inhibition suppressed this metabolic reprogramming and reduced tumor growth. Together, these findings define a hyperactive AR-LSD1 chromatin axis driven by minimal-length CAG repeats in AR and reveal a mechanistic link between inherited AR polymorphism, AR-mediated epigenetic–metabolic remodeling, and population-associated disparities in prostate cancer biology.","dates":{"publication":"2026/08/28"},"accession":"GSE310685","cross_references":{"GSM":["GSM9306710","GSM9306711","GSM9597071","GSM9597070","GSM9306712","GSM9597073","GSM9306713","GSM9306714","GSM9597072","GSM9306708","GSM9306709"],"GPL":["30173"],"GSE":["310685"],"taxon":["Homo sapiens"]}}