A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

Susanne Marije Kooistra, Lise Christine Rudkjær, 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 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.
Original languageEnglish
Article numbere91034
JournalPLOS ONE
Volume9
Issue number3
Pages (from-to)1-7
Number of pages7
ISSN1932-6203
DOIs
Publication statusPublished - 2014

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 105328749