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. 2024 Aug 6;15:6672. doi: 10.1038/s41467-024-50908-7

Fig. 6. Pharmacological inhibition of MAT2A by PF-9366 and AG-270 reverses the malignant transcriptome.

Fig. 6

A Schematic representation of the experimental procedure for RNA sequencing following drug treatment. B Number of genes deregulated in VCaP cells treated with PF-9366 or AG-270, compared to VCaP control cells. C Heatmap of differentially expressed genes in VCaP cells treated with either PF-9366 or AG-270, versus control VCaP cells. D PCA plot of VCaP cells, colored according to the conditions (CTRL, PF-9366 and AG-270). E Hallmark enrichment analysis of VCaP MAT2Akd (Sh1 and Sh2), VCaP treated with either PF-9366 or AG-270 versus respective control samples. Down-regulated pathways are colored in blue, up-regulated pathways are colored in red. F Convergence between MAT2Ai and MAT2Akd deregulated targets with threshold on Log2FC ± 0.1 (up-regulated and down-regulated genes as indicated). Top, overlap with genes deregulated by PF-9366. Bottom, overlap with genes deregulated by AG-270. G Functional annotation of convergent genes deregulated by AG-270, PF-9366 and MAT2Akd. Pathways upregulated and downregulated are shown in the left and right panel, respectively. Adjusted p-value ≤ 0.01. H Cumulative gene expression level of convergent up-regulated genes (1053) by PF-9366 and AG-270 and MAT2Akd in VCaP cells, in the cohort of primary, CRPC and NEPC patients. I Cumulative gene expression level of convergent down-regulated genes (963) by PF-9366 and AG-270, and MAT2Akd in VCaP cells, in the cohort of primary, CRPC and NEPC patients. Primary, n = 714; CRPC, n = 316; NEPC, n = 19. For box-and-whisker plots in H and I, the line inside the box shows the median value. The bounds of the box represent the 25th–75th percentiles, with whiskers at minimum and maximum values. One-way-ANOVA was used to test significant differences between groups. Panel A Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.