Article open access publication

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

PLoS ONE, Public Library of Science (PLoS), ISSN 1932-6203

Volume 9, 3, 2014

DOI:10.1371/journal.pone.0091034, Dimensions: pub.1028912031, PMC: PMC3961217, PMID: 24651706,

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Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU

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Denmark

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Europe

Description

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.

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University of Copenhagen

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Times Cited: 11

Field Citation Ratio (FCR): 1.26

Relative Citation ratio (RCR): 0.31

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Pure Gold