Myc: Maestro of MicroRNAs

Abstract

Hyperactivity of the Myc oncogenic transcription factor dramatically reprograms gene expression to facilitate cellular proliferation and tumorigenesis. To elicit these effects, Myc coordinates the activation and repression of an extensive network of protein-coding genes and, as has recently been appreciated, noncoding RNAs including microRNAs (miRNAs). Consistent with their ability to potently influence cancer phenotypes, the regulation of miRNAs by Myc affects virtually all aspects of the Myc oncogenic program, including proliferation, survival, metabolism, angiogenesis, and metastasis. This review will summarize the current understanding of the mechanisms underlying Myc-dependent transcriptional and posttranscriptional control of miRNAs and the resultant effects on tumorigenesis. As miRNAs are integral nodes in the transcriptional network controlled by Myc, modulating their activity represents a promising new approach for cancer therapy.

Figure 1.

Myc-mediated induction or repression of miRNAs impinges upon multiple phenotypes that contribute to tumorigenesis, including cell-cycle progression, apoptosis, metabolic reprogramming, angiogenesis, and metastasis.