Abstract
miR-21 is a microRNA (miRNA) frequently overexpressed in human cancers. Here we show that miR-21 is upregulated both in vitro and in vivo by oncogenic Ras, thus linking this miRNA to one of the most frequently activated oncogenes in human cancers. Ras regulation of miR-21 occurs with a delayed kinetic and requires at least two Ras downstream pathways. A screen of human thyroid cancers and non-small-cell lung cancers for the expression of miR-21 reveals that it is overexpressed mainly in anaplastic thyroid carcinomas, the most aggressive form of thyroid cancer, whereas in lung its overexpression appears to be inversely correlated with tumor progression. We also show that a LNA directed against miR-21 slows down tumor growth in mice. Consistently, a search for mRNAs downregulated by miR-21 shows an enrichment for mRNAs encoding cell cycle checkpoints regulators, suggesting an important role for miR-21 in oncogenic Ras-induced cell proliferation.
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Acknowledgements
We thank Pietro Carotenuto (CROM, Centro Ricerche Oncologiche Mercogliano, Italy), Ilaria Pedicelli (Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, Monaldi Hospital, Naples, Italy) and Nicolina De Rosa (Department of Pathology, Monaldi Hospital, Naples, Italy) for collection and technical help in the analysis of lung cancer samples. This work was supported by EU-Project-SIROCCO (Grant LSHG-CT-2006-037900), Associazione Italiana per la Ricerca sul Cancro (AIRC) to RDL and AIRC, EUFP7 Tumic to MZ.
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Frezzetti, D., Menna, M., Zoppoli, P. et al. Upregulation of miR-21 by Ras in vivo and its role in tumor growth. Oncogene 30, 275–286 (2011). https://doi.org/10.1038/onc.2010.416
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DOI: https://doi.org/10.1038/onc.2010.416
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