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

Kooistra, S. M., Nørgaard, L. C. R., Lees, M. J., Steinhauer, C., Johansen, J. V. & Helin, K., 2014, In : PLoS ONE. 9, 3, 7 p., e91034.

Research output: Contribution to journalArticleAcademicpeer-review

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

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.

Original languageEnglish
Article numbere91034
Number of pages7
JournalPLoS ONE
Volume9
Issue number3
Publication statusPublished - 2014

    Keywords

  • Cell Line, Cellular Senescence/genetics, Cyclin-Dependent Kinase Inhibitor p16/metabolism, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs/genetics, Oncogenes, RNA, Messenger/genetics

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