Transcriptome profiling of HepG2 cells upon treatment of the menin-MLL inhibitor MI-503 or DMSO

Hepatocellular carcinoma (HCC) accounts for the majority of malignant liver tumors and results in many deaths each year, emphasizing the need for new therapies. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Therefore, we performed RNA sequencing experiment to determine the transcriptome change in the HepG2 cells upon treatment of MI-503, a small molecule inhibitor of the menin-MLL1 interaction with optimized drug-like properties Overall design: HepG2 cells were plated in the 12-well plates at the initial concentration of 0.4x106 cells/ml and treated with 3 µM MI-503 or DMSO (0.25%) in triplicates. After 3 days of treatment viable cell number was adjusted to the original concentration in the DMSO treated samples and the same dilution factor was used to adjust cell number in the MI-503 treated cells. Media was changed and compound or DMSO was re-supplied at that time. Cells were harvested after 3 more days of incubation.

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Kempinska K, Malik B, Borkin D, Klossowski S, Shukla S, Miao H, Wang J, Cierpicki T, Grembecka J