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. Overall design: 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).