The quantitative analysis of transcriptomes derived from malignant rhabdoid tumor cells treated with EZH1/2 dual inhibitor or EZH2 selective inhibitor

We found that both EZH1 and EZH2 contributes to cell growth and H3K27 methylation, and EZH1/2 dual inhibitors induce growth inhibition in malignant rhabdoid tumor (MRT). To investigate the molecular mechanism underlying the growth inhibition of EZH inhibitors in MRT cells, we performed RNA-sequencing analysis and compared differentially expressed genes between A204.1 cells treated with EZH1/2 dual inhibitor DS-3201b or EZH2 selective inhibitor EPZ-6438. The comparisons of transcriptomes among EZH inhibitors (DS-3201b or EPZ-6438)-treated and non-treated (Control) A204.1 or TTC549 cells. A204.1 or TTC549 cells were treated with DS-3201b (100 nM) or EPZ-6438 (100 nM) for 14 days, followed by RNA-sequencing (RNA-seq) analysis.

本研究发现，EZH1与EZH2均可参与细胞增殖调控及H3K27甲基化过程，且EZH1/2双重抑制剂可诱导恶性横纹肌样瘤（malignant rhabdoid tumor, MRT）产生生长抑制效应。为探究EZH抑制剂对MRT细胞产生生长抑制的分子机制，本研究开展了RNA测序（RNA-sequencing）分析，对比经EZH1/2双重抑制剂DS-3201b或EZH2选择性抑制剂EPZ-6438处理的A204.1细胞的差异表达基因。本研究对经EZH抑制剂（DS-3201b或EPZ-6438）处理与未处理对照组（Control）的A204.1及TTC549细胞的转录组进行了对比分析。具体处理方案为：将A204.1或TTC549细胞以100 nM的DS-3201b或EPZ-6438处理14天，随后开展RNA测序（RNA-seq）分析。