The KDM5B lysine demethylase regulates androgen receptor function and expression in prostate cancer cells

KDM5B/JARID1B is an 2-oxoglutarate and Fe(2+) dependent oxygenase that demethylates the di- and tri-methylated histone H3 lysine 4 (H3K3) generally associated with transcriptional activation. KDM5B is also implicated in numerous pro-oncogenic mechanisms in many different types of cancer, including the hypoxic response, immune evasion and PI3/AKT signalling. We show that the CPI-455 KDM5B inhibitor impairs androgen regulated transcription and splicing. RNAseq was used to identify differentially expressed and spliced transcripts in LNCaP prostate cancer cells treated with androgen (R1881, 1nM) vs cells treated with both R1881 (1nM) and CPI-455 (50 µM).