Transcriptome profiling to explore the mechanism of the synthetic lethality. (A) and (B) REACTOME signal pathway analysis for the RNA sequencing results is shown. HCC1937 BRCA1 isogenic cells were treated with 5 μmol/L entinostat for 24 h and total RNA was extracted for RNA sequencing. The gene expression profiles were analyzed with REACTOME signal pathway database. The pathway genes that were significantly up- (A) and down-regulated (B) by entinostat are shown. (C) and (D) The effect of entinostat on cellular oxidative stress and DNA damage was examined. HCC1937 BRCA1−/− (C) or T47D shBRCA1 (D) cells were treated with 5 μmol/L entinostat for indicated time points and Western blots for proteins involved in oxidative stress and DNA damage responses were analyzed. GAPDH was used as an internal control. (E) RT-qPCR analysis for the TXNIP mRNA level was examined in HCC1937 BRCA1 isogenic cells treated with entinostat. (F) Chromatin immunoprecipitation (ChIP) of TXNIP promoter using anti-acetyl histone H4 antibody is shown. HCC1937 BRCA1−/− cells were treated with 5 μmol/L entinostat for 6 h and processed for ChIP using a rabbit IgG (control) or anti-acetyl histone H4 antibody. The ChIP DNA was subjected to PCR amplification with a primer pair specific for TXNIP promoter. (G) and (I) The effect of HDAC inhibitors, entinostat (class I-HDACi, G), vorinostat (pan-HDACi, H), and mocetinostat (class I-HDACi, I) on histone acetylation, cellular oxidative stress and DNA damage responses was examined in HCC1937 BRCA1 isogenic cell lines. Data are mean ± SD, *P < 0.05, **P < 0.01 between two groups.