Nuclear Export Mediated Regulation of MicroRNAs: Potential Target for Drug Intervention
Year: 2013
Type: article
Abstract: 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.
Source: Current Drug Targets
Authors: Irfana Muqbil, Bin Bao, Abdul Abou-Samra, Ramzi Mohammad, Asfar Azmi
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Funder: National Cancer Institute
OpenAlex ID: W2061492517