Figure 1 from Targeting PRMT5 Inhibitor–Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam

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Adaptation to PRMT5 inhibition involves upregulation of splicing factors. A, Scheme of RNA-seq experiment: DanG and PSN1 cells were treated for 72 hours with 20 nmol/L JNJ-64619178 or the vehicle control. RNA-seq data were analyzed by GSEA. B, Venn diagram of upregulated GO-BP gene sets in JNJ-64619178–treated DanG and PSN1 cells. C, GSEA (GeneTrail 3.2) results of GO-BP signatures in JNJ-64619178–treated vs. DMSO control DanG and PSN1 cells. Depicted are the top 14 enriched gene sets sorted by the lowest mean adjusted P value. Enrichment scores are shown on the x-axis. D, Venn diagram of JNJ-64619178 upregulated genes with a gene score >4 (GeneTrail 3.2) in the GO-BP mRNA metabolic process gene set. E and F, Heatmap of the 15 genes (D) upregulated in DanG (E) and PSN1 (F) cells by JNJ-64619178 treatment. G, Western Blot of RBM39 expression in PSN1 cells treated with PRMT5i JNJ-64619178 (4 nmol/L) or GSK-3326595 (200 nmol/L) or DMSO as the vehicle control for 24 and 48 hours. β-Actin was used as the loading control. One of three representative biological replicates is shown. H, Quantification of RBM39 expression (G) after 48 hours (n = 3). The intensity of antibody signal of RBM39 was normalized to the loading control. I and J, Western Blot of RBM39 protein expression in PSN1 (I) and BxPc3 (J) cells treated with increasing dosages of MRTX1719 for 48 hours. β-Actin was used as the loading control, and one of two (PSN1) or three (BxPc3) biological replicates is shown. K–N, Top, Western blot of RBM39 protein expression in PSN1 (K), DanG (L), MiaPaCa2 (M), and BxPc3 (N) cells treated with increasing dosages of TNG462 for 72 hours. β-Actin was used as the loading control. Bottom, quantification of three independent experiments. K, Friedman test P = 0.0009, *Dunn multiple-comparison test: P < 0.05; (L) Friedman test P = 0.015; (M) Friedman test P = 0.026; (N) Friedman test P = 0.038. [A, Created in BioRender. Schneider, G. (2026) https://BioRender.com/8or8uh9.]

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