Fig. 3: Indisulam resistance is associated with RBM39 upregulation and cell state switch from MES to ADRN in a C-MYC-overactive xenograft model.
From: RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity
a GSEA analysis of naïve (biological replicates n = 3) vs. relapsed tumors (biological replicates n = 3). Right y-axis indicates nominal p values (one-sided) and left y-axis indicates false discovery rate (FDR) q-values (one-sided with Benjamini-Hochberg method), and normalized enrichment score (NES) (x-axis). b-e GSEA shows “ADRN” and “neuronal system” gene sets. Nominal p values are calculated by one-sided Fisher’s exact test. f RBM39 and RBM23 expression in naïve (biological replicates n = 3) vs. resistant (biological replicates n = 3) SK-N-AS tumors. p values are calculated by two-sided Student t-test. g Volcano plot for differential peaks of ATAC-seq on or at nearby genes in resistant (biological replicates n = 4) vs naïve tumors (biological replicates n = 2). Y-axis = p values (two-sided, corrected by Benjamini-Hochberg method) transformed by -log10. X-axis = fold changes transformed by log2. Red =ADRN genes, Blue = MES genes. h Volcano plot for differential binding motifs of transcriptional factors. Y-axis indicates p values (two-proportion z-test) transformed by -log10 while x-axis indicates the fold changes of delta MD score. i Heatmap showing the motif displacement (MD) distribution of NFIA, ASCL1, SP2 and FOSL2, MD-score, and the number of this motif within 1.5 kb of an ATAC-seq peak naïve vs resistant tumors. j Volcano plot for differential peaks of H3K27Ac in naïve vs resistant tumors by CUT&Tag analysis. P value is two-sided, corrected by the Benjamini-Hochberg method. k GSEA analysis for genes with differential peaks of H3K27Ac in resistant (biological replicates n = 4) vs. naïve (biological replicates n = 2) tumors by CUT&Tag analysis. Blue indicates nominal P values (one-sided) and pink indicates false discovery rate (FDR) q values (two-sided, corrected by Benjamini-Hochberg method). l Heatmap indicates the binding motifs for transcriptional factors enriched in naïve, resistant and both based on Homer Motif analysis of H3K27Ac peaks. m IGV snapshots displaying the peaks in naïve vs resistant SK-N-AS cells by H3K27Ac CUT&Tag and ATAC-seq at RBM39 and RBM23 genomic loci. Source data are provided as a Source Data file.
