Fig. 6: Dissecting molecular mechanisms underlying the drug synergy of 11a and Romidepsin.
From: Orphan nuclear receptor NR2E3 is a new molecular vulnerability in solid tumors by activating p53
RNA-sequencing analysis of HeLa cells treated with DMSO, 150 nM 11a, 5 nM Romidepsin, or the combo for one day. A PCA plot indicated four well-separated sample clusters. B Heat map of the most differentially expressed genes in four groups. C Volcano plot of the transcripts of the combo vs DMSO. Red: growth inhibitory genes and black: growth promoting genes. The table summarized the number of differentially expressed genes in each comparison. D Up-regulations of five growth inhibitory genes were verified using qRT-PCR. p value was calculated by one-way Anova test and Bonferroni post-hoc test (DMSO vs 11a vs Romidepsin vs Combo). *p < 0.0083; **p < 0.00167; ***p < 0.00017. E Up-regulations of p53-targeted genes were examined in HeLa cells using Immunoblotting assay. HeLa cells were treated with DMSO, 150 nM 11a, 5 nM Romidepsin, or the combo for one day. F GSEA plots of p53 pathway in the indicated comparison. G Heat map of differentially expressed genes in the p53 pathway among 4 groups. H Up-regulations of p53 pathway genes were verified using qRT-PCR. p value was calculated by one-way Anova test and Bonferroni post-hoc test (DMSO vs 11a vs Romidepsin vs Combo). *p < 0.0083; **p < 0.00167; ***p < 0.00017. I GSEA plots of MYC pathway in the indicated comparison. J Heat map of differentially expressed genes in the MYC pathway among 4 groups. K Down-regulations of MYC pathway genes were verified using qRT-PCR. p value was calculated by one-way Anova test and Bonferroni post-hoc test (DMSO vs 11a vs Romidepsin vs Combo). *p < 0.0083; **p < 0.00167; ***p < 0.00017. L Four drug synergy modes were identified by multiple comparisons of GSEA. Mean ± SD shown in all the histograms.
