miRNA interplay: mechanisms and consequences in cancer

ABSTRACT Canonically, microRNAs (miRNAs) control mRNA expression. However, studies have shown that miRNAs are also capable of targeting non-coding RNAs, including long non-coding RNAs and miRNAs. The latter, termed a miRNA:miRNA interaction, is a form of self-regulation. In this Review, we discuss the three main modes of miRNA:miRNA regulation: direct, indirect and global interactions, and their implications in cancer biology. We also discuss the cell-type-specific nature of miRNA:miRNA interactions, current experimental approaches and bioinformatic techniques, and how these strategies are not sufficient for the identification of novel miRNA:miRNA interactions. The self-regulation of miRNAs and their impact on gene regulation has yet to be fully understood. Investigating this hidden world of miRNA self-regulation will assist in discovering novel regulatory mechanisms associated with disease pathways.