BioScientifica, Endocrine-Related Cancer, 5(21), p. R409-R429, 2014
DOI: 10.1530/erc-14-0208
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Hormones are key drivers of cancer development. To date, interest has largely focussed on the classical model of hormonal gene regulation but there is increasing evidence for a role of hormone signalling pathways in post-translational regulation of gene expression. In particular, a complex and dynamic network of bi-directional interactions with microRNAs at all stages of biogenesis and during target gene repression is emerging. MicroRNAs, which act mainly by negatively regulating gene expression through association with 3' untranslated regions of mRNA species, are increasingly understood to be important in development, normal physiology and pathogenesis. Given recent demonstrations of altered microRNA profiles in a diverse range of cancers, their ability to function as oncogenes or tumour suppressors, and hormonal regulation of microRNAs, understanding mechanisms by which microRNAs are generated and regulated is vitally important. MicroRNAs are transcribed by RNA polymerase II then processed in the nucleus by the Drosha-containing Microprocessor complex and in the cytoplasm by Dicer, before mature microRNAs are incorporated into the RNA-induced silencing complex. It is increasingly evident that multiple cellular signalling pathways converge upon the miR biogenesis cascade, adding further layers of regulatory complexity to modulate miR maturation. This review summarises recent advances in identification of novel components and regulators of the Microprocessor and Dicer complexes, with particular emphasis on the role of hormone signalling pathways in regulating their activity. Understanding hormone regulation of microRNA production and how this is perturbed in cancer is critical for the development of microRNA-based therapeutics and biomarkers.