Identification And Functional Annotation Of Genome-wide AR-regulated Genes In Prostate Cancer Based On ChIP-Seq Data

As a member of Nuclear Receptor Superfamily, Androgen Receptor (AR) is animportant steroid receptor. The most important role of AR is acting as a DNA-bindingtranscript factor which regulates gene expression. AR is an important therapy target ofprostate cancer, but the mechanism of action is still unclear. In this study, we annotatedthose AR binding gens in the genome by ChIP-Seq data, and tried to discover some novelbiological pathways in prostate cancer. Analysis on6ChIP-Seq datasets from threeprostate cancer cell lines indicated that83.46%of AR binding sites were located in theintron region; the other16.54%located in the promoter, enhancer, exon,3’UTR,5’UTR,downstream and intergenic region, respectively. In the promoter region we found4novelAR binding motifs. The enrichment analysis of AR-binding genes identified21GeneOntology terms，1KEGG pathway and26GeneGo pathways. The pair-wise overlapanalysis for AR binding genes and AR related pathways verified the hypothesis that thesignificant signatures of different data sets are more similar at pathway level than at genelevel. Literature validation of26GeneGo pathways demonstrated that5pathways had beenreported previously, the rest21are novel pathways. We also verified association of thesenovel pathways and prostate cancer by prostate cancer related gene expression data andmicroRNA data.