Kooistra, Susanne Marije6; Rudkjær, Lise Christine6; Lees, Michael James7; Steinhauer, Cornelia7; Johansen, Jens Vilstrup8; Helin, Kristian6
1 Helin Group, BRIC Research Groups, BRIC, Københavns Universitet2 Robot Section, BRIC Laboratories, BRIC, Københavns Universitet3 Core facilities, BRIC Laboratories, BRIC, Københavns Universitet4 Department of Biology, Faculty of Science, Københavns Universitet5 The Danish Stem Cell Center, Faculty of Health and Medical Sciences, Københavns Universitet6 Helin Group, BRIC Research Groups, BRIC, Københavns Universitet7 Robot Section, BRIC Laboratories, BRIC, Københavns Universitet8 Core facilities, BRIC Laboratories, BRIC, Københavns Universitet
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 p16INK4A 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.