期刊
ONCOGENE
卷 30, 期 3, 页码 275-286出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2010.416
关键词
microRNA; miR-21; Ras; anaplastic thyroid carcinoma; non-small-cell lung cancer
资金
- EU [LSHG-CT-2006-037900]
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- AIRC, EUFP7 Tumic
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. Oncogene (2011) 30, 275-286; doi:10.1038/onc.2010.416; published online 18 October 2010
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