Fig. 3: Loss of ARID1A elevates cell cycle signalling in Pten-deficient tumours.

a Number of significant genes (P < 0.05, Fold Change >1.5) from RNA-Seq analysis of endpoint prostate tumours comparing Pb-Cre;Ptenfl/fl Arid1a+/+ (n = 3) compared to Pb-Cre;Ptenfl/fl Arid1afl/+ (n = 3) or Pb-cre;Ptenfl/fl Arid1afl/fl (n = 3) mice. b Principal component analysis (PCA) showing comparison and variance of individual mouse samples of indicated cohorts. c Volcano plot showing up and downregulated genes (P < 0.05, Fold Change >1.5) in Ptenfl/fl Arid1afl/+ (n = 3) and Ptenfl/fl Arid1afl/fl (n = 3) cohorts. d Significantly upregulated cell signalling networks visualised using Metacore in Pb-Cre;Ptenfl/fl Arid1afl/fl compared to Pb-Cre;Ptenfl/fl Arid1a+/+ tumours. e Gene set enrichment analysis showing 1.58 normalised enrichment score (NES) in Hallmark G2M checkpoint from Pb-Cre;Ptenfl/fl Arid1afl/fl mice. Most significant genes of enrichment shown in heatmap with z-score indicated between +2 and –2 with colour gradient of red to blue. f Fold change in cell count for DU145 EV clones compared to ARID1A KO clones after 72 h of growth, *P = 0.015, **P = 0.0025, ****P < 0.0001; ANOVA with Tukey’s analysis. Each data point represents a single technical replicate, three of which made up each experimental replicate, error bars showing SE. g Stain intensity of colony growth from colony forming assay. Relative growth relative to EV1. *P = 0.02 EV1 vs KO2, *P = 0.045 EV1 vs KO4, ANOVA with Tukey’s analysis. Each point represents an experimental replicate each made up of three technical replicates, error bars showing SEM. h Number of significant genes (P < 0.05, Fold Change >1.5) from RNA-Seq analysis comparing EV1 (n = 5) compared to KO2 (n = 5) or KO4 (n = 5). Principle component analysis (PCA) showing comparison and variance of individual samples of indicated cell clones. i Significantly upregulated cell signalling networks visualised using Metacore in KO2 and KO4 compared to EV1. j Gene set enrichment analysis showing 1.59 (KO2) and 1.84 (KO4) normalised enrichment score (NES) in Hallmark Mitotic Spindle compared to EV1. Genes from leading edge of enrichment shown in heatmap with z-score indicated between +2 and –2 with colour gradient of red to blue.