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

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    Abstract

    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
    DOIs
    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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