MicroRNA, nutrition, and cancer prevention

Abstract

MicroRNA (miRNA) are small noncoding RNA molecules that are involved in post-transcriptional gene silencing. Alterations in miRNA expression are observed in and may underlie many different human diseases, including cancer. In fact, miRNA have been shown to affect the hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Genetic and epigenetic alterations may explain aberrant miRNA expression in cancer cells and may also contribute to cancer risk. It is now thought that by circulating through the bloodstream, miRNA can exert their effects at distant sites as well as within the cells of origin. Recent evidence suggests that nutrients and other bioactive food components protect against cancer through modulation of miRNA expression. Moreover, dietary factors have been shown to modify miRNA expression and their mRNA targets in various cancer processes, including apoptosis, cell cycle regulation, differentiation, inflammation, angiogenesis, and metastasis as well as pathways in stress response. Herein, we provide a brief overview of dietary modulation of miRNA expression and its potential role in cancer prevention. Understanding the affect of dietary factors on miRNA expression and function may provide insight on prevention strategies to reduce the burden of cancer.

FIGURE 1

Cellular biogenesis, export, and circulation of miRNA. miRNA are processed from precursor molecules via a 2-step mechanism. In the nucleus, the enzyme Drosha processes the pri-miRNA to pre-miRNA hairpins, which are exported to the cytoplasm. Once in the cytoplasm, the pre-miRNA is either further processed by the RNA polymerase Dicer and unwound to yield mature miRNA or exported to other cells through the bloodstream. Mature miRNA are assembled into the RISC. The miRNA-RISC complex regulates post-transcriptional expression by targeting specific mRNA for degradation or translational inhibition. For cell export, pre-miRNA are thought to be packaged into exosomes and/or multivesicular bodies and transported into the bloodstream. These circulating miRNA are thought to be taken up by recipient cells by either endocytosis or receptor binding and processed into mature miRNA to inhibit the expression of target protein-coding genes in the recipient cell. Ago2, Argonaute 2; miRNA, microRNA; pre-miRNA, precursor microRNA; pri-miRNA, precursor primary microRNA; RISC, RNA-induced silencing complex; TRSP, (or TARBP2) trans-activation-responsive RNA-binding protein.

FIGURE 2

Aberrant miRNA expression affects signaling pathways to enhance tumorigenesis. Representative miRNA are depicted that have been shown to act as oncogenes or tumor suppressor genes to affect the 6 common hallmarks of cancer. miRNA, microRNA.