The synthetic lethal relationship between MYC and SAE2 has been previously described in FC-MYC cells using RNAi (Littler et al., 2019). Building on this work, we conducted transcriptomic analysis on MYC-low and MYC-high cells following inhibition of SUMOylation with the SAE1/2 inhibitor, ML-792 (SAEi). FC-MYC cells were grown for twenty-four hours in the absence (MYC-low) and presence (MYC-high) of 500ng/mL tetracycline and treated with either DMSO (vehicle control) or 25 nM SAEi for 24 hours. Three biological replicates were performed for RNAseq analysis, with additional subsets of cells reserved for complementary analyses, including DNA content profiling by flow cytometry and MYC protein expression analysis through western blotting. DNA content analysis showed that SAEi treatment had minimal affect on MYC-low cells but induced polyploidy and apoptosis in MYC-high cells. Western blotting confirmed MYC expression at the protein level as expected. This dataset provides transcriptomic profiles of MYC-low and MYC-high cells under SUMOylation inhibition, offering insights into the differential impact of SAEi on different MYC backgrounds. The dataset also includes analysis of parental RKO cells exposed to the SAEi.
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