Figure 4

Genome-wide analysis for response to gemcitabine and ISRIB. PNAC-1 cells were incubated for 36 h in the absence or presence of 10 μM Gem 0.5 μM ISRIB, and collected RNA was used for RNA transcriptome sequencing. (a) Total number of genes with significant change in gene expression (>1.5-folds increase or <−1.5-fold decrease, P<0.001) following indicated incubations compared with control are represented in a Venn diagram. (b) Heat map for fold changes in gene expression (P<0.001) over control following indicated incubations is shown for genes involved in the ISR pathway. ISR genes and gene expression data from RNA-seq analysis are shown. (c) ISR genes with more than 2-fold change in gene expression (P<0.001) in response to Gem compared with control are shown. (d) IPA was performed on obtained RNA-seq data and major canonical signaling pathways that were modulated in response to drugs are represented. (e) Heat map for fold changes in gene expression (P<0.001) over control condition following indicated incubations is shown for genes involved in eIF2 signaling. Network of genes involved in eIF2 signaling was collected from IPA as described in Materials and Methods. (f) Top 20 genes that are differentially regulated in response to Gem alone versus Gem+ISIRB are shown (P<0.001)