Fig. 9: Therapeutic targeting of CRPC in vivo. | Nature Communications

Fig. 9: Therapeutic targeting of CRPC in vivo.

From: Intron retention is a hallmark and spliceosome represents a therapeutic vulnerability in aggressive prostate cancer

Fig. 9

a Schematic of in vivo E7107 treatment. b–e Inhibitory effects of E7107 on the growth of indicated Enza-resistant CRPC models in vivo. Shown are the tumor growth curves (left; insets present tumor randomizations), endpoint tumor images (middle), and tumor weight (right) of LAPC9-AI (b, c; n = 4 for each group), LNCaP-AI (d; n = 5 and 8 for vehicle and treatment group, respectively), and PC3 (e; n = 6 for each group) models treated with vehicle or E7107. Data represent mean ± SD and all P-values were determined by two-tailed unpaired Student’s t-test. f, g Effect of E7107 on CRPC transcriptome in vivo. Shown are schematic of RNA-seq experiment (f) and the ratio of total DSEs (g; left) and total DEGs (g; right) identified upon E7107 treatment in indicated CRPC models. h AS pattern showing that E7107 reshapes the splicing landscape of CRPC xenografts in vivo. i Sashimi plots and RT-PCR validation of IR in DDIT3 gene after E7107 treatment in vivo. For RT-PCR, three independent experiments were performed with two loaded in the gel. The event ΔPSI values calculated by rMATS were provided in parentheses. E, E7107; V, vehicle; M, DNA marker. In the gel images, the sizes of GAPDH and the upper (with intron retention) and lower bands of DDIT3 mRNA were 148, 459, and 192 bp, respectively. Source data are provided as a Source Data file.

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