Fig. 2: AR-regulated gene expression signature in CRPC tissues.

a Workflow for identifying AR-regulated genes in three prostate cancer cell lines. We used AR ChIP-seq and RNA-seq data in three prostate cancer cell lines to determine AR-binding genes induced or repressed by androgen or AR. We selected RefSeq genes with AR-binding sites within 50 kb from transcription start sites (TSSs) as AR-binding genes. For RNA-seq, LNCaP and VCaP cells were treated with DHT 10 nM or vehicle to analyze the regulation by androgen. 22Rv1 cells were treated with siRNA targeting AR (siAR) or control siRNA (siControl) to evaluate the effect of AR on gene expression levels. Thus we selected genes with AR bindings as well as regulated by androgen or AR as AR-target genes. b Summary of the expression changes of AR-induced genes. Rate of AR-induced genes in LNCaP/VCaP and 22Rv1 cells overlapped with genes upregulated in CRPC compared with Pca tissues significantly (Up in CRPC), upregulated in Pca compared with benign and downregulated in CRPC compared with Pca tissues significantly (Up in Pca/Down in CRPC), or other genes upregulated in Pca significantly (Up in Pca) are shown. Chi-square test was performed to analyze whether the difference is significant. c Expression profile of AR-induced genes upregulated in Pca compared with benign prostate tissues are shown as heatmaps. Top 200 highly expressed AR-induced genes (LNCaP/VCaP and 22Rv1 cells) in Pca tissues are shown. d AR regulation of representative CRPC marker genes. AR-binding signals and active histone modification signals (AcH3, K4me3) in 22Rv1 cells obtained by ChIP-seq were summarized. UBE2C, EZH2, and CDK1 are shown as representative genes. ChIP-seq signals relative to input control are shown. e Gene Ontology (GO) term analysis of AR-regulated genes in 22Rv1 cells.