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Review
. 2012 Dec;6(6):590-610.
doi: 10.1016/j.molonc.2012.09.006. Epub 2012 Oct 9.

MicroRNA and cancer

Affiliations
Review

MicroRNA and cancer

Martin D Jansson et al. Mol Oncol. 2012 Dec.

Abstract

With the advent of next generation sequencing techniques a previously unknown world of non-coding RNA molecules have been discovered. Non-coding RNA transcripts likely outnumber the group of protein coding sequences and hold promise of many new discoveries and mechanistic explanations for essential biological phenomena and pathologies. The best characterized non-coding RNA family consists in humans of about 1400 microRNAs for which abundant evidence have demonstrated fundamental importance in normal development, differentiation, growth control and in human diseases such as cancer. In this review, we summarize the current knowledge and concepts concerning the involvement of microRNAs in cancer, which have emerged from the study of cell culture and animal model systems, including the regulation of key cancer-related pathways, such as cell cycle control and the DNA damage response. Importantly, microRNA molecules are already entering the clinic as diagnostic and prognostic biomarkers for patient stratification and also as therapeutic targets and agents.

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Figures

Figure 1
Figure 1
miRNA deregulation in cancer. A schematic representation depicting the canonical miRNA biogenesis pathway and the general mechanisms whereby normal miRNA expression and function can be deregulated in cancer. (A) Deregulation of miRNA gene transcription in cancer through genetic, epigenetic and transcriptional mechanisms. Active transcription is indicated by green arrow, blocked transcription by red block arrow. Red crosses indicate loss of gene, epigenetic mechanism or transcription factor. Me, methylation; Ac, acetylation. [Refer to Sections 3.1–3.3 in main text.] (B) Simplified canonical pathway of miRNA biogenesis and processing. Steps commonly deregulated in cancer indicated in red. [Sections 1 and 3.4] (C) Mechanisms prevalent in cancer allowing mRNAs to escape regulation by miRNAs. RNA binding protein abbreviated as RBP. ceRNAs represented in blue. [Section 3.5].
Figure 2
Figure 2
Functions of p53. This diagram depicts the activation and functions of the p53 tumour suppressor and their cellular effects. (A) Key proteins participating in the activation and posttranscriptional control of p53 in response to cellular stress are shown. [Refer to Section 4.3 in main text.] (B) Functions of p53 dependant on its role as a transcription factor are summarised here. Representative examples of p53 activated proteins and miRNAs are shown, as are a selection of targets for each miRNA. [Sections 3.3.2, 4.3.3] (C) Transcription‐independent functions of p53 relying on its participation in protein–protein interactions. Examples of miRNAs upregulated post‐transcriptionally by p53 and a selection of their target genes are shown. Examples of apoptotic regulators bound by p53 are shown. [Sections 3.3.2, 4.3.3].
Figure 3
Figure 3
Regulation of p53 by miRNAs. Left: miRNAs directly repressing p53 through binding to sites in the p53 3′UTR. Right: Examples of miRNAs positively regulating p53 through repression of a selection of other targets that antagonise p53 function. Block arrows indicate repression. Feedback loops where p53 is also capable of increasing the miRNA levels are indicated with arced arrows. [Refer to Sections 3.3.2, 4.3.1, 4.3.3 in main text].

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