CTBP2 represses MYC-IRF4 transcriptional network in MM. (A-B) Differentially expressed genes (DEGs) after CTBP2 transduction in MM.1S and NCI-H929 cells. Genes with an absolute fold change >1.5 and adjusted-P < .05 relative to control cells were included. (A) Venn diagram of DEGs showing the number of overlap and unique genes in HMCL. (B) Volcano plots illustrating common DEGs upon CTBP2 transduction. Red dots indicate upregulated genes and blue dots indicate downregulated genes. Important downstream targets of CTBP2 were labeled with gene symbols and chosen for further study. (C) GSEA of hallmark gene sets ranked by normalized enrichment scores. Bubble plot showing top gene sets with downregulated patterns with false discovery rate (FDR) <0.05. The size and color of each bubble represent the number of DEGs in each pathway and the FDR, respectively. (D) GSEA showing downregulation of MYC and E2F hallmark gene sets upon CTBP2 transduction in MM. (E) Gene expression profiling of MYC and MYC-dependent genes (n = 83) in transduced MM cells with the MYC target PCR array. Change in gene expression was calculated using the ΔΔCt method. Yellow, relatively low expression; blue, relatively high expression. (F) Transcript levels of MYC and its targets evaluated by real-time quantitative polymerase chain reaction. GAPDH served as the reference gene. (G) Immunoblotting analysis illustrating the downregulation of MYC and its targets in CTBP2-transduced MM cells compared with EV. β-actin served as the internal control. (H) GSEA of the previously described IRF4 gene sets. Bubble plot showing downregulation of IRF4 targets upon CTBP2 transduction. All pathways with FDR <0.001. (I-J) Exogenous expression of MYC rescued MM cells from CTBP2-induced growth inhibition in (I) MM.1S and (J) NCI-H929 cells, as shown by (from left to right) WST-1 assay showing cell growth at day 4 relative to day 0, and transduction efficiency for MYC and CTBP2 demonstrated at the mRNA and protein levels. In panels F,I,J, results are expressed as mean ± SD of triplicate measurements from at least 3 independent experiments. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.

CTBP2 represses MYC-IRF4 transcriptional network in MM. (A-B) Differentially expressed genes (DEGs) after CTBP2 transduction in MM.1S and NCI-H929 cells. Genes with an absolute fold change >1.5 and adjusted-P < .05 relative to control cells were included. (A) Venn diagram of DEGs showing the number of overlap and unique genes in HMCL. (B) Volcano plots illustrating common DEGs upon CTBP2 transduction. Red dots indicate upregulated genes and blue dots indicate downregulated genes. Important downstream targets of CTBP2 were labeled with gene symbols and chosen for further study. (C) GSEA of hallmark gene sets ranked by normalized enrichment scores. Bubble plot showing top gene sets with downregulated patterns with false discovery rate (FDR) <0.05. The size and color of each bubble represent the number of DEGs in each pathway and the FDR, respectively. (D) GSEA showing downregulation of MYC and E2F hallmark gene sets upon CTBP2 transduction in MM. (E) Gene expression profiling of MYC and MYC-dependent genes (n = 83) in transduced MM cells with the MYC target PCR array. Change in gene expression was calculated using the ΔΔCt method. Yellow, relatively low expression; blue, relatively high expression. (F) Transcript levels of MYC and its targets evaluated by real-time quantitative polymerase chain reaction. GAPDH served as the reference gene. (G) Immunoblotting analysis illustrating the downregulation of MYC and its targets in CTBP2-transduced MM cells compared with EV. β-actin served as the internal control. (H) GSEA of the previously described IRF4 gene sets. Bubble plot showing downregulation of IRF4 targets upon CTBP2 transduction. All pathways with FDR <0.001. (I-J) Exogenous expression of MYC rescued MM cells from CTBP2-induced growth inhibition in (I) MM.1S and (J) NCI-H929 cells, as shown by (from left to right) WST-1 assay showing cell growth at day 4 relative to day 0, and transduction efficiency for MYC and CTBP2 demonstrated at the mRNA and protein levels. In panels F,I,J, results are expressed as mean ± SD of triplicate measurements from at least 3 independent experiments. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal