Disruption of microRNA nuclear transport in human cancer

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. MicroRNAs target about 80% of the protein-coding mRNAs and therefore can be considered master regulators of multiple cellular pathways, contributing to the fine-tuning the cell's most important processes, like the ones involved in cellular growth and proliferation. Deregulation of miRNAs plays a fundamental role in the onset, progression and dissemination of many cancers; therefore impairment of miRNA biosynthesis is an important event in the tumorigenic cascade. MicroRNA synthesis is a multistep regulated process that requires transport of RNA molecules from the nucleus to the cytoplasm. The immature miRNA species that are produced in the nucleus are exported through the nuclear pore complexes via mobile export receptors. Small RNAs such as precursors of miRNAs (pre-miRNAs) are transported out of the nucleus by a specific nuclear transport receptor, exportin-5 (XPO5). Pre-miRNA nuclear export is a fundamental step in miRNAs biosynthesis and its deregulation through inactivating mutations in the XPO5 gene can lead to pre-miRNA nuclear accumulation and disturbance of mature miRNA expression. In addition, it is becoming increasingly evident that mature miRNAs also function as gene regulators in the nuclear compartment. In this review, we will discuss the export of miRNA precursors and its impairment in human cancer as well as the recently described nuclear functions of miRNAs.