PLoS ONE (Jan 2014)

A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.

  • Susanne Marije Kooistra,
  • Lise Christine Rudkjær Nørgaard,
  • Michael James Lees,
  • Cornelia Steinhauer,
  • Jens Vilstrup Johansen,
  • Kristian Helin

DOI
https://doi.org/10.1371/journal.pone.0091034
Journal volume & issue
Vol. 9, no. 3
p. e91034

Abstract

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Oncogene-induced senescence (OIS) can occur in response to hyperactive oncogenic signals and is believed to be a fail-safe mechanism protecting against tumorigenesis. To identify new factors involved in OIS, we performed a screen for microRNAs that can overcome or inhibit OIS in human diploid fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16(INK4A) and senescence-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA.