Fig. 5: Prediction of essentiality of UAP1 in MM with gmctool.
From: An automated network-based tool to search for metabolic vulnerabilities in cancer
a Selected gMCS: {UAP1, UAP1L1} and gene expression in our cohort of, MMRF-CoMMpass and selected MM Cell Lines. We include for each patient in the MMRF-CoMMpass cohort whether they involve the translocation t(4;14). b Boxplot of expression of the UAP1 and UAP1L1 genes in the B-cell differentiation (n = 5 for NB, n = 7 for CB, n = 7 for CC, n = 8 for MEM, n = 5 for TPC, n = 3 for BMPC, n = 31 for MM.non.responder and n = 6 for MM.responder), MMRF-CoMMpass (n = 660 for MM.non.responder and n = 107 for MM.responder) and MM Cell Lines (n = 5 for MM.non.responder and n = 3 for MM.responder). In the boxplots, the center line represents the median, the bounds of the box correspond to the 25th and 75th percentiles, the whiskers indicate the interquartile range by 1.5 times, and the circles are the outliers. c Correlation between the essentiality of UAP1 (CRISPR knockout screen data, DepMap) and the expression of UAP1L1 in log2(TPM + 1) (n = 851). Error bands denote the 95% confidence interval of the predicted values obtained from a linear regression model. Pearson correlation coefficient (ρ) and two-sided correlation test p-value are shown. d qPCR-RT of UAP1 and UAP1L1 expression in OPM-2 and JJN-3 cell lines. Data are referred to GUS gene. Data are presented as mean values of three experimental replicates. e Proliferation of UAP1-deficient OPM-2 and JJN-3 cell lines with two different siRNAs. The proliferation percentage refers to cells nucleofected with negative control siRNA (Scramble, black line). Data represent mean ± standard deviation of three experimental replicates; Note: ****/ns refer to the statistical significance level from an unpaired one-sided Wilcoxon test, respectively ****: p-value ≤ 0.0001 and ns: non-significant. Source data are provided as a Source Data file. BMPC bone marrow plasma cells, TPC tonsil plasma cells, MEM memory B cells, CC centrocytes, CB centroblasts, NB naïve B cells (NB), MM.responder MM samples sensitive to UAP1 inhibition, MM.non.responder MM samples resistant to UAP1 inhibition.
