Fig. 9: Transcriptional inhibition waves induced by synthetic ecteinascidins in melanoma and SCLC cells. | Nature Communications

Fig. 9: Transcriptional inhibition waves induced by synthetic ecteinascidins in melanoma and SCLC cells.

From: Pan-inhibition of super-enhancer-driven oncogenic transcription by next-generation synthetic ecteinascidins yields potent anti-cancer activity

Fig. 9

a, b Heatmap showing average 18S-normalized expression (n = 3) of the indicated genes in 501mel a and MM029 b cells treated with either lurbinectedin, ecubectedin or PM54 (5xIC50 concentration) for the indicated period of time. Results were obtained by RT-qPCR and are shown as relative expression compared to DMSO-treated cells. RPL13a is a housekeeping gene. c Heatmap showing average 18S-normalized expression (n = 3) of the indicated genes in DMS53 cells (SCLC) treated with synthetic ecteinascidins (5xIC50 concentration (IC50 = 0.11 nM for lurbinectedin, 0.16 nM for ecubectedin and 0.15 nM for PM54)) for the indicated period of time. Results were obtained by RT-qPCR and are shown as relative expression compared to DMSO-treated cells. RPL13a is a housekeeping gene. d Upper panel: This analysis (n = 3) focuses on three gene sets: (1) genes commonly downregulated after treatment in melanoma, SCLC, and NSCLC cells, (2) putative super-enhancer-dependent genes in DMS53 SCLC cells, and (3) genes whose expression exhibited a fold change between 0.9 and 1.1 relative to DMSO, which we considered unaffected by the treatment (GSE195663). These sets comprised 648, 424, and 8435 genes, respectively. From these genes, we selected only the genes presenting H3K27ac peaks located at their transcription start sites (TSS), yielding 348 genes for the commonly downregulated genes across the three cancers, 424 for the SCLC super-enhancer-dependent genes, and 1434 for the unaffected genes (see Supplementary Data 7). Metaplot distribution shows H3K27ac signal in a ± 5 kb window around the TSS of these three groups of genes in mock- or lurbinectedin-treated DMS53 cells (GSE179074). Lower panel: Heatmap profiles representing the read density clusters obtained with seqMINER for the H3K27ac signal. e Gene tracks showing H3K27ac occupancy and RNA-Seq signals (n = 3) at the CDK8 (top), MYC (middle) and RPL13a (bottom) loci in mock- or lurbinectedin-treated DMS53 cells.

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