MYC, microRNAs and glutamine addiction in cancers.

The MYC oncogene encodes a transcription factor, c-Myc (Myc), which is a master regulator of cell metabolism and proliferation. Myc directly influences the expression of thousands of genes, of which, subsets are coordinately regulated with other transcription factors under specified conditions. Myc regulates entry into S phase by stimulating glucose and glutamine metabolism and mitochondrial biogenesis that are coupled to the regulation of E2F1 expression. As a transcription factor, Myc regulates genes involved in these pathways either transcriptionally or post-transcriptionally through direct regulation of microRNA expression. Myc's de-regulation of the expression of glutamine transporters and miR-23a/b that targets glutaminase, triggers an addiction to glutamine, which is required for bioenergetics, nucleotide biosynthesis and redox homeostasis in cancer cells. The induction of the miR-17 cluster by Myc attenuates E2F1 protein expression, such that interruption of this regulatory loop results in DNA replication stress. Hence, deregulated Myc expression in cancers is accompanied by key nodal points that could be exploited for therapeutic purposes.