GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310689/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310689GEOGSEfalseMinimal-length CAG repeats in AR define a hyperactive AR-LSD1 axis driving metabolic reprogramming in prostate cancer [RNA-Seq]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.2026/08/28GSE310689GSM9306919GSM9306921GSM9306920GSM9306923GSM9306922GSM9306925GSM9306924GSM9306927GSM9306926GSM9306918GSM9306929GSM930692830173310689Homo sapiens