MicroRNA biogenesis pathways in cancer

Key Points MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene expression through mRNA degradation or translational inhibition. The miRNA biogenesis pathway is a multi-step process that has a crucial role in regulating miRNA maturation. miRNAs can be oncogenes or tumour...

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Published in:Nature reviews. Cancer Vol. 15; no. 6; pp. 321 - 333
Main Authors: Lin, Shuibin, Gregory, Richard I.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-06-2015
Nature Publishing Group
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Summary:Key Points MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene expression through mRNA degradation or translational inhibition. The miRNA biogenesis pathway is a multi-step process that has a crucial role in regulating miRNA maturation. miRNAs can be oncogenes or tumour suppressors and are globally repressed in cancers. Mutations in or dysregulation of components of the miRNA biogenesis pathway are frequently found in cancers and have important functions in oncogenesis. Important oncogenic signalling proteins — such as LIN28A, LIN28B, epidermal growth factor receptor (EGFR) and Hippo — target miRNA biogenesis in cancers. The targeting of abnormal miRNA biogenesis pathways is a novel, promising therapeutic strategy for cancers. The microRNA (miRNA) biogenesis pathway is frequently altered in cancer, leading to global downregulation of miRNA levels in some cancer types. This Review discusses the alterations that affect miRNA biogenesis in cancer. MicroRNAs (miRNAs) are critical regulators of gene expression. Amplification and overexpression of individual 'oncomiRs' or genetic loss of tumour suppressor miRNAs are associated with human cancer and are sufficient to drive tumorigenesis in mouse models. Furthermore, global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic. This, together with the recent identification of novel miRNA regulatory factors and pathways, highlights the importance of miRNA dysregulation in cancer.
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ISSN:1474-175X
1474-1768
DOI:10.1038/nrc3932