Upregulation of miR-21 by Ras in vivo and its role in tumor growth

D. Frezzetti, M. De Menna, P. Zoppoli, C. Guerra, A. Ferraro, A. M. Bello, P. De Luca, C. Calabrese, A. Fusco, M. Ceccarelli, M. Zollo, M. Barbacid, R. Di Lauro, G. D. Vita

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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.

Original languageEnglish
Pages (from-to)275-286
Number of pages12
JournalOncogene
Volume30
Issue number3
DOIs
Publication statusPublished - 20 Jan 2011

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Keywords

  • Ras
  • anaplastic thyroid carcinoma
  • miR-21
  • microRNA
  • non-small-cell lung cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Frezzetti, D., De Menna, M., Zoppoli, P., Guerra, C., Ferraro, A., Bello, A. M., De Luca, P., Calabrese, C., Fusco, A., Ceccarelli, M., Zollo, M., Barbacid, M., Di Lauro, R., & Vita, G. D. (2011). Upregulation of miR-21 by Ras in vivo and its role in tumor growth. Oncogene, 30(3), 275-286. https://doi.org/10.1038/onc.2010.416