Fig. 1

CARM1-expressing EOC cells are selectively sensitive to EZH2 inhibitors. a Expression of CARM1, EZH2, and Cyclin A in the indicated EOC cell lines, HOSE, and FTE cells were determined by immunoblot. Expression of β-actin was used as a loading control. b Expression of CARM1 and a loading control β-actin in CARM1-high parental and CRISPR-mediated CARM1 knockout (KO) A1847 cells. c Equal number of parental control or CARM1 knockout A1847 cells were plated and treated with each of the 23 individual epigenetic inhibitors for 14 days. The media with the inhibitors was refreshed every 3 days. Cell growth was quantified as integrated density using NIH ImageJ software. Quantification of the average integrated density graphed as a scatter plot. The X-axis indicates the relative growth of treated CARM1 knockout A1847 cells compared with DMSO vehicle controls. Y-axis indicates the relative growth of treated CARM1-high parental A1847 cells compared with DMSO vehicle controls. n = 4; error bars represent SEM. d Representative images of colonies formed by the cells treated with the indicated inhibitors. GSK126 and UNC1999 represent positive hits from the screen. Note that CI994 was used a negative control that showed no difference between parental and CARM1 knockout cells. e Expression of CARM1, H3K27Me3, EZH2, and H3 in parental control and CARM1 knockout A1847 cells. f Relative expression of EZH2 in the TCGA HGSOC cases with (n = 61) or without (n = 467) CARM1 amplification. Relative EZH2 expression levels were transformed to log₂ (10+ expression) values. P-values are from two-tailed t-test. Error bars represent SD