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

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 2 — A Number of genes affected by knockdown of MAT2A (Sh1 and Sh2) in VCaP cells (p-value ≤ 0.05). B Principal component analysis (PCA) plot of VCaP cell lines, colored according to the condition (Ctrl, Sh1, Sh2). C Heatmap of differentially expressed genes in MAT2Akd (VCaP Sh1 and VCaP Sh2) versus control VCaP cells (VCaP Ctrl). Replicates (n = 3 biological replicates) are indicated. D Hallmark enrichment analysis of MAT2Akd VCaP cells (Sh1 and Sh2) compared to control cells, performed with cameraPR function. Down-regulated pathways are colored in blue, up-regulated pathways are colored in red. E Functional annotation of top-ranking features of MAT2Akd VCaP cells (Sh1 and Sh2) performed with enrichR (cell markers augmented). F Fold changes of selected oncogenic drivers in MAT2Akd cells (Sh1 and Sh2) versus VCaP control, evaluated by RNA-seq. G Cumulative gene expression level of down-regulated genes in MAT2Akd VCaP cells (Sh1 and Sh2) in the cohort of primary (n = 714), CRPC (n = 316) and NEPC (n = 19) patients. H Fold changes of selected canonical androgen genes in MAT2Akd (Sh1 and Sh2) versus VCaP control cells evaluated by RNA-seq. I Cumulative gene expression level of up-regulated genes in MAT2Akd VCaP cells (Sh1 and Sh2) in the cohort of primary (n = 714), CRPC (n = 316) and NEPC (n = 19) patients. J Venn diagram showing the overlap between down-regulated genes in VCaP MAT2Akd cells (Sh1 and Sh2) and gene set associated with NEPC. Test: Fisher exact test. Fold changes of selected NEPC (K) and cancer stem cell genes (L), repressed by MAT2Akd in VCaP cells (Sh1 and Sh2). M Hallmark enrichment analysis of ERG + MAT2A RWPE-1 cells compared to RWPE-1 MAT2A performed with cameraPR function. Down-regulated pathways are colored in blue, up-regulated pathways are colored in red. N Fold change of selected CSC- and EMT-related genes up-regulated in RWPE-1 ERG + MAT2A versus RWPE-1 MAT2A. For box-and-whisker plots in G 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.