Fig. 2: Co-regulation of pyrimidine synthesis genes by ERG and GOF mutant p53 in GEM prostate tumors and human PCa cell line.

a Venn diagram showing the overlap between the genes upregulated in prostate tumors of Pb-T2-ERG;Trp53pcR172H/- mice (n = 3, 15 months old) and those upregulated in prostatic tissues of Pb-T2-ERG;Trp53pc-/- mice (n = 3, 15 months old) revealed by RNA-seq data. b Venn diagram showing the overlap between the genes (n = 901) uniquely upregulated in prostate tumors of Pb-T2-ERG;Trp53pcR172H/- mice (n = 3, 15 months old) as defined in (a) and ERG-bound gene targets identified by ChIP-seq in murine prostate tumors (GSM1145303). c Heatmap of RNA-seq data showing a subset of genes (n = 531) differentially expressed in the benign or cancerous prostate tissues of mice (15 months old) with the indicated genotypes (n = 3 except the Trp53pcR172H/- single mutant group and Pb-T2-ERG;Trp53pc-/- group). d KEGG pathway analysis of 531 ERG target genes that were uniquely upregulated in prostate tumors of Pb-T2-ERG;Trp53pcR172H/- mice as shown in (c). e Diagram depicting the key enzymes including UMPS, RRM1, RRM2 and TYMS in pyrimidine synthesis. f UCSC Genome Browser screenshots in the Umps gene locus showing the results of RNA-seq data from the benign or cancerous prostate tissues of mice (15 months old) with the indicated genotypes (n = 3 except the Trp53pcR172H/- single mutant group) and the ERG ChIP-seq data from murine prostate tumors (GSM1145303). g Heatmap of RNA-seq data showing expression of the indicated PSGs in the benign or cancerous prostate tissues of mice (15 months old) with the indicated genotypes. h RT-qPCR analysis of expression of the indicated PSGs in the benign or cancerous prostate tissues of mice (15 months old) with the indicated genotypes. i RT-qPCR analysis of indicated proteins and PSG gene mRNAs in VCaP cells stably expressing control (shcon) or gene-specific shRNAs. Data in (h) and (i) were shown as mean ± s.d. from three independent experiments. Two-tailed Student’s t test was performed in (h) and (i).