Fig. 2: Transcriptome analyses in TAK-931-treated HeLa cells.
a Venn diagrams of upregulated genes in TAK-931-treated cells. HeLa cells were treated with DMSO or TAK-931 for 24 h (green), 48 h (blue), or 72 h (red). The upregulated genes (>1.5 of log2[TAK-931/DMSO]) were determined at each time point. b Top eight enriched KEGG terms in 72 h TAK-931-treated HeLa cells. Orange indicates inflammatory cytokine-related pathways. KEGG pathway analysis using DAVID, one-sided p-values for Fisher’s Exact test is adopted to measure the gene-enrichment in annotation terms. c GSEAs of representative inflammation-related terms. The RNA-seq data of HeLa cells after 72 h treatment with DMSO or TAK-931 were used. d Subextractor network analysis of the upregulated genes in 48 h (left) and 72 h (right) TAK-931-treated HeLa cells. The network was visualized using Cytoscape (v3.1.2). e The enrichment network colored by the p-values of upregulated genes in 48 h (upper) and 72 h (lower) TAK-931 treatments. f Cross-network analysis of upregulated genes between 48 h and 72 h TAK-931 treatments. g Heatmaps of individual genes in the enriched cytokine-cytokine receptor interaction pathway. The cells are colored according to their TPM. h Experimental schemes for sequential combination treatment with TAK-931 and sapanisertib. i Growth inhibition curves in combination treatment with TAK-931 and sapanisertib in HeLa cells at the indicated concentrations. Data are presented as mean ± SD (n = 4 independent experiments). j 3D plots illustrating Loewe Additivity in combination treatment with TAK-931 and sapanisertib. Positive and negative synergistic scores were colored by red and green, respectively. Source data are provided as a Source Data file.
