Analysis of whole genome expression change after NPD13668 treatment

EZH2 is a catalytic component of polycomb repressive complex 2 (PRC2), which contributes to aggressiveness in many types of cancers. Targeting EZH2/PRC2 has been challenged and now some inhibitors are under clinical trials for cancer treatments. Interestingly, anti-tumor effects of EZH2 is not always depend on H3K27 methyltransferase activity. In order to identify novel inhibitors against EZH2/PRC2, we established a chemical screening system based on measurement of reactivation of promoter activity, which is intrinsically silenced by EZH2/PRC2. We screened more than 300,000 small chemicals and identified 85 chemicals. After validation of reactivation of EZH2/PRC2 target genes, we identified chemical NPD13668 as a potential inhibitor of EZH2/PRC2 activity. To evaluate NPD13668 effect, we analysed whole genome expression change by using SurePrint G3 Human GE 8×60K array slides (G4851B, Agilent Technologies). Microarray experiment was performed as single-color hybridization on SurePrint G3 Human GE 8×60K array.