Fig 1: CDK8 regulates mTOR signaling in MYC-driven medulloblastoma.a. Gene set variation analysis of patient samples (n=763) revealed that the MYC-overexpressing subtypes Group3β and 3γ were enriched with gene sets of MYC and mTOR signaling. b. Multiplex IHC on G3-MB patient samples using CDK8, p-4EBP1, c-MYC, RPS12, p-S6, and p-AKT antibodies. p<0.05 in all biomarker groups. Scale bar, 100 μm. Statistical analysis: unpaired t-test. c. GSEA plots of representative gene sets involved in mTOR signaling following CDK8 depletion. Normalized enrichment score (NES) and false discovery rate (FDR) are indicated. d. Immunoblot showing the levels of p-4EBP1 and p-S6 following CDK8 knockdown. e. Immunoblot showing the levels of p-4EBP1 and p-S6 upon treatment with RVU120. f. Representative bioluminescence images of mice treated with TAK-228 (1mg/kg, daily, oral gavage) compared with those of the control cohort. g. Kaplan–Meier survival curves for animals treated with control or TAK-228. Statistical analysis: Log-rank test. h. IHC analyses of cleaved caspase 3 in xenografts mice. Three mice from each group were sacrificed 18 days after tumor implantation. Original magnification, ×40.