Fig. 6: JUN promotes tumor growth of FOXA2-driven PCa models.
From: FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer
a, b GSEA for differentially regulated genes in PC-3 (a) or NCI-H660 (b) transfected with siNTC versus siFOXA2 or siJUN (RNA-seq data). The red color indicates enriched pathways for downregulated genes by FOXA2 or JUN silencing. c, d BETA for the association of JUN binding sites with JUN-regulated genes in PC-3 (c) or NCI-H660 (d) cells. e, f Boxplot view for the expression (Log2(CPM_zscore)) of JUN-activated genes (n = 1036 genes for PC-3, n = 132 genes for NCI-H660) in PC-3 or NCI-H660 cells transfected with siNTC versus siFOX2 (e), or treated with/out ORY-1001 (10 μM for 24 h) (f) (center: median; box: 25th to 75th IQR; whiskers: 1.5x IQR; outliers: individual data points; statistical significance determined by unpaired two-sided t-test). g qRT-PCR for the expression levels of indicated FOXA2-JUN cotargets in PC-3 cells treated with siFOXA2, siJUN, siFOSL1, or siNTC (n = 3 independent samples; data represented as mean ± SEM, statistical significance determined by unpaired two-sided t-test). h Kaplan–Meier curve for the overall survival from the start of a first-line ARSi in CRPC tumors (SU2C dataset, n = 106) with higher FOXA2-JUN co-target signature (red, the top 25%) versus lower (blue, the bottom 75%). i Cell viability assay for LNCaP and PC-3 cells treated with 0–100 μM T5224, an AP-1 inhibitor, for 3d (LNCaP, n = 5 independent samples; PC-3, n = 4 independent samples; data represented as mean ± SEM; statistical significance determined by two-way ANOVA). j, k PC-3 (j) or NCI-H660 (k) cells were subcutaneously injected into male mice. Mice bearing parental tumors were then treated with T5224 (6 mg/kg, 5 days per week via gavage). Tumor growth was measured at indicated time points (PC-3, n = 12 independent tumors; NCI-H660, n = 8 independent tumors; data represented as mean ± SEM; statistical significance determined by two-way ANOVA). ns (P > 0.05), *(0.01 < P < 0.05), **(0.001 < P < 0.01), ***(P < 0.001), and ****(P < 0.0001) were used to indicate the levels of P-value. Source data are provided as a Source Data file.
