Fig. 4: BA inhibits the transcription of multiple genes related to treatment resistance. | British Journal of Cancer

Fig. 4: BA inhibits the transcription of multiple genes related to treatment resistance.

From: Benzaldehyde suppresses epithelial-mesenchymal plasticity and overcomes treatment resistance in cancer by targeting the interaction of 14-3-3ζ with H3S28ph

Fig. 4

a Hierarchical clustering of changes in gene expression for BxPC-3, AsPC-1, and PANC1 cells treated with BA at 100 or 500 μM for 24 h compared with DMSO-treated control cells, as determined by microarray analysis. The heat map includes genes that showed a log2[fold change] of ≥1 or ≤–1 in BxPC-3 cells treated with 500 μM BA. SFRS1 (SRSF1), LIN28B, ID1, E2F8, and E2F2 genes are labeled on the right side of the heat map with their respective probe set IDs. b Pathways upregulated (red bars, top) or downregulated (blue bars, bottom) by treatment with 500 µM BA in BxPC-3 cells. Bar length indicates –log10[adjusted p value]. c Heat map of changes in E2F family gene expression in the three cell lines treated with BA. The map shows log2[fold change] values. d RT-qPCR analysis of E2F2 mRNA in parental (P-) BxPC-3 cells treated with 500 µM BA or DMSO for 20 h. e RT-qPCR analysis of E2F2 mRNA in P-BxPC-3 and osimertinib-resistant (O-) BxPC-3 cells treated with 500 µM BA or DMSO for 20 h. f RT-qPCR analysis of E2F2 mRNA in O-BxPC-3 cells expressing WT or S28A mutant forms of histone H3 and treated with 500 µM BA or DMSO for 20 h. g Schematic illustration of the proposed mechanism for regulation of E2F2 transcription by H3S28ph under the stress condition induced by osimertinib treatment and for the effect of BA. h RT-qPCR analysis of E2F2 mRNA in P-BxPC-3 and radiation-resistant (R-) BxPC-3 cells treated with DMSO for 20 h. i RT-qPCR analysis of LIN28B mRNA in P-A549 cells treated with 500 µM BA or DMSO for 20 h. j RT-qPCR analysis of LIN28B mRNA in A549 cells expressing 14-3-3ζ shRNAs or in control (shCtrl) cells treated with 500 µM BA or DMSO for 20 h. k RT-qPCR analysis of E2F8 mRNA in A549 cells treated with 500 µM BA or DMSO for 20 h. l RT-qPCR analysis of E2F8 mRNA in A549 cells as in j. All RT-qPCR data are means ± SD from three independent experiments. **p < 0.01,***p < 0.001; ns: not significant (two-tailed Student’s t test or one-way ANOVA followed by Tukey’s multiple-comparison test). m Schematic illustration of the proposed mechanism for regulation of the transcription of LIN28B, E2F8, and other genes by BA and 14-3-3ζ. Sphere-forming assay in A549 cells incubated with 500 µM BA or DMSO for 4 days: n Microscopic findings of the spheroid, o CellTiter-Glo assay (n = 6). ****p < 0.0001 (two-tailed Student’s t test).

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