Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08907 L'Hospitalet, Barcelona, Catalonia, Spain; Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain.
Semin Cancer Biol. 2014 Aug;27:46-51. doi: 10.1016/j.semcancer.2014.02.012. Epub 2014 Mar 7.
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.
微小 RNA（miRNAs）是一种小型非编码 RNA，可在后转录水平调控基因表达。miRNAs 靶向约 80%的蛋白质编码 mRNAs，因此可以被认为是多种细胞途径的主要调控因子，有助于微调细胞最重要的过程，如参与细胞生长和增殖的过程。miRNAs 的失调在许多癌症的发生、发展和扩散中起着至关重要的作用；因此，miRNA 生物合成的损害是肿瘤发生级联反应中的一个重要事件。miRNA 的合成是一个多步骤调控的过程，需要 RNA 分子从细胞核运输到细胞质。在细胞核中产生的不成熟 miRNA 物种通过核孔复合物通过移动的出口受体被运出。小 RNA（如 miRNA 的前体（pre-miRNA））通过特定的核转运受体（exportin-5，XPO5）从细胞核中运出。pre-miRNA 的核输出是 miRNA 生物合成的基本步骤，通过 XPO5 基因的失活突变导致 pre-miRNA 的核积累和成熟 miRNA 表达的紊乱。此外，越来越明显的是，成熟的 miRNAs 也作为核区室中的基因调节剂发挥作用。在这篇综述中，我们将讨论 miRNA 前体的输出及其在人类癌症中的失调，以及最近描述的 miRNAs 的核功能。
