Fig. 6: Schematic representation of the downstream effects of EZH2i on the metabolic profile of sensitive MM cell lines.
From: A distinct metabolic response characterizes sensitivity to EZH2 inhibition in multiple myeloma
A UNC1999 inhibits the activity of EZH2. B This prevents EZH2 from methylating H3, thus resulting in loss of H3K27me3 and open chromatin. As a consequence, the tumour-suppressor miRNAs miR-494-39, miR-192-5p, miR-130a-3p and miR-134-5p, which are silenced by H3K27me3 under basal conditions, are upregulated. C The tumour-suppressor miRNAs downregulate their target genes (MAT2A, MAT2B, CBS and CTH), which encode for enzymes involved in methionine cycling. This dysregulates methionine cycling and results in variation of metabolite abundance, such as accumulation of homocysteine. Metabolites in each pathway are indicated by small circles, which are colour coded with the same colour of the pathway they participate in. Metabolites that vary in abundance post UNC1999 treatment are marked by either a red (decreased abundance) or a green (accumulation) border.
