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.
Keywords: XPO5, XPO1, CRM1, nuclear export, small molecule inhibitors, selective inhibitors of nuclear export.
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