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

N R Christoffersen, R Shalgi, Lisa Frankel, Eleonora Leucci, Michael James Lees, Mikkel Klausen, Y Pilpel, F C Nielsen, M Oren, A H Lund

303 Citationer (Scopus)


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.
TidsskriftCell Death and Differentiation
Udgave nummer2
Sider (fra-til)236-45
Antal sider10
StatusUdgivet - 1 feb. 2010


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