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  • Review Article
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Metastamirs: a stepping stone towards improved cancer management

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that regulate protein expression. Aberrant miRNA expression in cancer has been well documented; miRNAs can act as oncogenes or tumor-suppressor genes, depending on the cellular context and target genes that they regulate, and are involved in tumor progression and metastasis. The potential mechanisms by which miRNAs are involved in tumor aggressiveness include migration, invasion, cell proliferation, epithelial-to-mesenchymal transition, angiogenesis and apoptosis. MiRNAs are involved in various cellular pathways and an miRNA can elicit more than one biological effect in a given cell. Existing data show the potential clinical utility of miRNAs as prognostic and predictive markers for aggressive and metastatic cancers. The stability of miRNAs in formalin-fixed, paraffin-embedded tissues and body fluids is advantageous for biomarker discovery and validation. In addition, miRNAs can be extracted from small biopsy specimens, which is a further advantage. Finally, miRNAs are potential therapeutic agents for personalized cancer management.

Key Points

  • MiRNAs can act as oncogenes or tumor-suppressor genes

  • MiRNAs have differential expression, both upregulation and downregulation, in tumor progression and metastasis

  • MiRNAs have an effect on a number of pathways that contribute to metastasis, including migration, invasion, cell proliferation, epithelial-to-mesenchymal transition, angiogenesis and apoptosis

  • One miRNA can have an effect on different metastasis-contributing pathways and its expression can be regulated by different proteins

  • The clinical applications of miRNAs include their use as prognostic markers for survival, and as predictive markers for treatment efficiency, enhancing our move into the era of personalized medicine

  • MiRNAs are unique candidates for targeted therapy owing to their capacity to simultaneously affect multiple molecules along the same pathway

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Figure 1: Diagrammatic representation of the effect of miRNAs on metastasis.
Figure 2: The complex involvement of miR-21 in multiple cell-signaling pathways.

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Acknowledgements

We would like to thank R. Kirk for her careful and precise review and critical comments to improve the manuscript. This work was supported by grants to G. M. Yousef from the Canadian Institute of Health Research (CIHR grant #86490), Canadian Cancer Society (CCS grant #20185), and the Ministry of Research and Innovation, Government of Ontario.

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N. M. A. White, E. Fatoohi and M. Metias researched the data for the article. All the authors provided a substantial contribution to discussions of the content. N. M. A. White and G. M. Yousef contributed to writing the article and N. M. A. White, M. Metias, K. Jung, C. Stephan and G. M. Yousef reviewed and/or edited the manuscript before submission.

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Correspondence to George M. Yousef.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Metastasis-promoting miRNAs in tumor progression and metastasis (DOC 82 kb)

Supplementary Table 2

Metastasis-inhibiting miRNAs in tumor progression and metastasis (DOC 84 kb)

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White, N., Fatoohi, E., Metias, M. et al. Metastamirs: a stepping stone towards improved cancer management. Nat Rev Clin Oncol 8, 75–84 (2011). https://doi.org/10.1038/nrclinonc.2010.173

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