MicroRNAs (
miRNAs) are short non-coding RNAs that have been recognized to regulate the expression of uncountable number of genes. Their aberrant expression has been found to be linked to the pathology of many diseases including
cancer. There is a drive to develop
miRNA targeted
therapeutics for different diseases especially
cancer. Nevertheless, reining in these short non-coding RNAs is not as straightforward as originally thought. This is in view of the recent discoveries that
miRNAs are under epigenetic regulations at multiple levels.
Exportin 5
protein (XPO5) nuclear export mediated regulation of
miRNAs is one such important epigenetic mechanism. XPO5 is responsible for exporting precursor
miRNAs through the nuclear membrane to the cytoplasm, and is thus a critical step in
miRNA biogenesis. A number of studies have shown that variations in components of the
miRNA biogenesis pathways, particularly the aberrant expression of XPO5, increase the risk of developing
cancer. In addition to XPO5, the
Exportin 1 protein (XPO1) or chromosome region maintenance 1 (CRM1) can also carry
miRNA export function. These findings are supported by pathway analyses that reveal certain
miRNAs as direct interaction partners of CRM1. An in depth understanding of
miRNA export mediated regulatory mechanisms is important for the successful design of clinically viable
therapeutics. In this review, we describe the current knowledge on the mechanisms of
miRNA nuclear transport mediated regulation and propose strategies to selectively block this important mechanism in
cancer.