title: A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
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.
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Susanne Marije
authors.initials: SM
authors.lastname: Kooistra
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lise Christine Rudkjær
authors.initials: LC
authors.lastname: Nørgaard
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael James
authors.initials: MJ
authors.lastname: Lees
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Steinhauer
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens Vilstrup
authors.initials: JV
authors.lastname: Johansen
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark; The Danish Stem Cell Center (DanStem), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger