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. Author manuscript; available in PMC: 2012 Nov 29.
Published in final edited form as: Nature. 2012 Feb 15;482(7385):347–355. doi: 10.1038/nature10888

Figure 1. Mechanisms of miRNA perturbation in cancer.

Figure 1

Cancer cells present global downregulation of miRNAs, loss of tumour-suppressor miRNAs and specific accumulation of oncogenic miRNAs. The alteration in miRNA expression patterns leads to the accumulation of oncogenes and downregulation of tumour-suppressor genes, which leads to the promotion of cancer development. a, The expression and function of oncogenic miRNAs is increased by genomic amplification, activating mutations, loss of epigenetic silencing and transcriptional activation. By contrast, tumour-suppressor miRNAs are lost by genomic deletion, inactivating mutations, epigenetic silencing or transcriptional repression. b, After transcription, global levels of miRNAs can be reduced by impaired miRNA biogenesis. Inactivating mutations and reduced expression have been described for almost all the members of the miRNA processing machinery. If there is a downreguation of DROSHA this can lead to a decrease in the cropping of primary miRNA (pri-miRNA) to precursor miRNA (pre-miRNA). In the case of XPO5 mutation, pre-miRNAs are prevented from being exported to the cytoplasm. Mutation of TARBP2 or downregulation of DICER1 results in a decrease in mature miRNA levels. Pol II, RNA polymerase II; RISC, RNA-induced silencing complex.