Contribution of UPF1  and RCOR1 to androgen response of prostate cancer cells.
The ligand-activated androgen receptor is a transcription factor that drives prostate cancer growth. Blocking androgen-activation of androgen receptor via androgen deprivation therapy is the default treatment for metastatic prostate cancer. Despite initial remissions, androgen deprivation invariably fails and prostate cancer progresses to castration-recurrent disease, which still relies on aberrantly activated androgen receptor. Alternative approaches are needed to inhibit androgen receptor action in prostate cancer that has failed androgen deprivation therapy. Our laboratory has been exploring the therapeutic potential of a non-canonical androgen receptor signaling mechanism wherein androgen receptor stimulates another transcription factor, Serum Response Factor. Serum Response Factor-mediated androgen receptor action correlates with prostate cancer progression and is enriched in castration-recurrent prostate cancer. Inhibiting Serum Response Factor-dependent androgen receptor action may be an effective treatment strategy following failure of androgen deprivation therapy but remains poorly understood. We have recently isolated UPF1 and RCOR1 as putative novel mediators of Serum Response Factor-dependent androgen receptor action.  Here, we perform RNA-Seq assays to determine the contribution of UPF1 and RCOR1 to the androgen response of prostate cancer cells. Overall design: LNCaP cells were transfected with siGenome SmartPools (Horizon Discovery)  against UPF1, RCOR1 or non-targeting control siRNA. The next day, medium was changed to androgen-deprived medium. At 48h post transfection, androgen-deprived medium was refreshed and cells were treated with 5nM R1881 or vehicle (ethanol). Biological triplicates were included in each treatment group. Cells were harvested in Trizol reagent at 48h after treatment.