Linus Pauling Institute

There is growing interest in the epigenetic mechanisms that impact human health and disease, including the role of microRNAs (miRNAs). These small (18-25 nucleotide), evolutionarily conserved, non-coding RNA molecules regulate gene expression in a post-transcriptional manner. Several well-orchestered regulatory mechanisms involving miRNAs have been identified, with the potential to target multiple signaling pathways dysregulated in cancer. Since the initial discovery of miRNAs, there has been progress towards therapeutic applications, and several natural and synthetic chemopreventive agents also have been evaluated as modulators of miRNA expression in different cancer types. This review summarizes the most up-to-date information related to miRNA biogenesis, and critically evaluates proposed miRNA regulatory mechanisms in relation to cancer signaling pathways, as well as other epigenetic modifications (DNA methylation patterns, histone marks) and their involvement in drug resistance. We also discuss the mechanisms by which dietary factors regulate miRNA expression, in the context of chemoprevention versus therapy.