Journal
CELL DEATH AND DIFFERENTIATION
Volume 17, Issue 2, Pages 236-245Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2009.109
Keywords
miRNA; miR-34a; B-RAF; senescence; MYC
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Funding
- EC [201102]
- Vilhelm Pedersen and Hustrus Foundation
- Danish National Research Foundation
- Danish Medical Research Council
- Danish Cancer Society
- Association for International Cancer Research
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Aberrant oncogene activation induces cellular senescence, an irreversible growth arrest that acts as a barrier against tumorigenesis. To identify microRNAs (miRNAs) involved in oncogene-induced senescence, we examined the expression of miRNAs in primary human TIG3 fibroblasts after constitutive activation of B-RAF. Among the regulated miRNAs, both miR-34a and miR-146a were strongly induced during senescence. Although members of the miR- 34 family are known to be transcriptionally regulated by p53, we find that miR-34a is regulated independently of p53 during oncogene-induced senescence. Instead, upregulation of miR-34a is mediated by the ETS family transcription factor, ELK1. During senescence, miR-34a targets the important proto-oncogene MYC and our data suggest that miR-34a thereby coordinately controls a set of cell cycle regulators. Hence, in addition to its integration in the p53 pathway, we show that alternative cancer-related pathways regulate miR-34a, emphasising its significance as a tumour suppressor. Cell Death and Differentiation (2010) 17, 236-245; doi:10.1038/cdd.2009.109; published online 21 August 2009
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