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Oncomirs — microRNAs with a role in cancer

Key Points

  • MicroRNAs (miRNAs) are an abundant class of negative gene regulators that have been shown to control a wide range of biological functions such as cellular proliferation, differentiation and apoptosis.

  • About half of the annotated human miRNAs map within fragile regions of chromosomes, which are areas of the genome that are associated with various human cancers.

  • Recent evidence indicates that miRNAs can function as tumour suppressors and oncogenes, and they are therefore referred to as 'oncomirs'. Factors that are required for the biogenesis of miRNAs have also been associated with various cancers and might themselves function as tumour suppressors and oncogenes.

  • Expression profiling of miRNAs has been shown to be a more accurate method of classifying cancer subtypes than using the expression profiles of protein-coding genes. The differential expression of certain miRNAs in various tumours might become a powerful tool to aid in the diagnosis and treatment of cancer.

  • Gene therapies that use miRNAs might be an effective approach to blocking tumour progression. miRNAs such as let-7, which has been shown to negatively regulate the Ras oncogenes, and miR-15 and miR-16, which negatively regulate BCL2, are promising candidates for cancer treatment.

Abstract

MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.

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Figure 1: The biogenesis of microRNAs.
Figure 2: MicroRNAs can function as tumour suppressors and oncogenes.

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Acknowledgements

We thank Helge Grosshans and Diya Banerjee for critical reading of the manuscript. F.J.S. is supported by grants from the National Science Foundation and the National Institutes of Health and A.E.-K. is supported by a Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship.

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National Cancer Institute

breast cancer

Burkitt lymphoma

cervical cancer

colorectal tumours

glioblastoma

hepatocellular carcinoma

Hodgkin lymphoma

leukaemia

lung cancer

multiple myeloma

ovarian cancer

pancreatic cancer

prostate cancer

renal tumours

stomach cancer

testicular cancer

urothelial cancer

Wilms tumour

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Glossary

Fragile site

A site in a chromosome that is susceptible to chromosome breakage, amplification and fusion with other chromosomes. This can be induced by exposure to inhibitors of DNA replication, such as aphidicolin, and there are more than 80 commonly described sites.

Bead-based flow cytometry

A technique that is used to profile miRNA gene expression and miRNA abundance. This method couples oligonucleotides that are complementary to the miRNAs of interest onto polystyrene beads that are impregnated with a variable mixture of two fluorescent dyes (yielding 100 colours to differentiate up to 100 individual miRNAs). Purified miRNAs from tissue samples are hybridized to the oligo-coupled beads and the fluorescent intensity is measured using a flow cytometer.

Anti-miRNA oligonucleotides

Oligonucleotides of about 22 nucleotides that are complementary to a given miRNA sequence and can specifically inhibit miRNA activity. RNA modifications that are made to the ribose group and target the 2′ position (such as in 2′-O-methyl oligos or those with a 2′-O, 4′-C-methylene bridge) increase the stability, efficacy and affinity of the oligonucleotide.

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Esquela-Kerscher, A., Slack, F. Oncomirs — microRNAs with a role in cancer. Nat Rev Cancer 6, 259–269 (2006). https://doi.org/10.1038/nrc1840

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