Fig. 4

Chemical inhibition of CDK12/13 deeply impaired the DDR in MYC-driven Group 3 MB cells. A Bar graphs showing RNA expression levels of the indicated DDR genes in Group 3 MB patients compared to fetal (FC) and adult cerebellum (AC) from EGA RNA-seq expression dataset (EGAD00001004958). Welch's t-test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001); n.s. stands for not significant. B Boxplot showing RNA expression of the indicated genes in Group 3 MB patients grouped according to the 3 molecular subtypes (α, β, γ) derived from the publicly available dataset Cavalli. Welch's t-test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001). C Bar graphs showing the results of qPCR analyses for the expression of DDR genes in MB cells, as indicated. Data are expressed as fold change relative to DAOY set as 1. mRNA expression is normalized on GAPDH expression. Graphs show the mean ± SD of 3 independent experiments. One-Way ANOVA (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001); n.s. stands for not significant. Black and red asterisks indicate statistical analysis performed versus DAOY or ONS-76, respectively. D Bar graphs showing the results of qPCR analyses for the expression of MYC and DDR genes in D341 cells depleted for MYC expression by siRNAs-mediated silencing. mRNA expression is normalized on GAPDH expression. Graphs show the mean ± SD of 3 independent experiments. Unpaired t-test (**p < 0.01, ***p < 0.001). E Bar graphs showing the results of qPCR analyses for the expression of DDR genes in D341 cells after treatment with 100 nM THZ531 for 8 h. mRNA expression is normalized on GAPDH expression. Graphs show the mean ± SD of 3 independent experiments. Unpaired t-test (***p < 0.001; ****p < 0.0001)