A model of the GIs between Myc, its targets, and miRNAs in normal and tumor cells. In normal cells, multiple miRNAs are expressed that can repress Myc or Myc targets. miRNA genes are not repressed by Myc because of the low levels of Myc signaling in normal cells. Tumor cells acquire diverse genetic or epigenetic alterations that result in the overexpresssion of Myc and Myc targets to facilitate tumor development through diverse cellular processes. On one hand, Myc can be amplified and overexpressed. On the other hand, miRNAs are silenced by genetic (loss of heterozygosity), epigenetic (hypermethylation), or regulatory (repression by Myc) mechanisms. Because of the low levels of these miRNAs, signaling by Myc and Myc targets is enhanced resulting in dramatic deregulation of the cell cycle, protein translation, and metabolism among other cellular processes. This model is mostly based on the results obtained by Chang et al19 on the repression of miRNAs by Myc and the control of Myc by miRNAs reported here.
