p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC

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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.
Original languageEnglish
JournalCell Death and Differentiation
Volume17
Issue number2
Pages (from-to)236-45
Number of pages10
ISSN1350-9047
DOIs
Publication statusPublished - Feb 2010

    Research areas

  • Cell Aging, Cell Cycle, Cell Division, Cell Line, Transformed, Fibroblasts, Humans, MicroRNAs, Neoplasms, Oncogenes, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-myc, Tumor Suppressor Protein p53, Up-Regulation, ets-Domain Protein Elk-1

ID: 50503724