Fig. 3.

Effect of antisense oligonucleotide (AON)-intronic splicing enhancer (ISE) on androgen receptor (AR)-V7-targeted gene expression. a Microarray analysis showing AR, UBE2C, and BUB1B gene expression profiles in normal prostate (NP, n = 7), benign prostate hyperplasia (BPH, n = 12), primary prostate cancer (PCa, n = 49), castration-resistant prostate cancer (CRPC, n = 22), and metastasis (n = 7). Microarray values (2 log scale are shown as the mean ± SD of each group is depicted. Unpaired t-test; **p < 0.01; ***p < 0.001). b Pearson correlation of AR-FL, AR-V7, UBE2C, and BUB1B mRNA expression, obtained by RT-qPCR, in CRPC (n = 20) specimens. Two-tailed p-values and Pearson r values are depicted. NS; p > 0.05. c Relative UBE2C and BUB1B mRNA expression in VCaP cells, determined 96 h after treatment with 0.1 nM R1881, or R1881 in combination with 2 µM enzalutamide. Unpaired t-test; *p < 0.05; **p < 0.01; ***p < 0.001. Bars represent the mean ± SD of three independent experiments. d Relative mRNA expression levels of AR-V7, UBE2C, and BUB1B in VCaP cells following transfection with an AR-V7 expression vector. Unpaired t-test; *p < 0.05; ***p < 0.001). Bars represent the mean ± SD of three independent experiments. e, f Relative mRNA expression from AR-V7 (e), UBE2C and BUB1B (f) in DuCaP and VCaP cells, as determined 96 h after treatment with increasing doses of AON-ISE, compared with non-transfected cells (NT). Unpaired t-test; *p < 0.05; **p < 0.01; ***p < 0.001. Bars represent the mean ± SD of three independent experiments