A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.

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 fibrob...

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Autores principales:	Susanne Marije Kooistra, Lise Christine Rudkjær Nørgaard, Michael James Lees, Cornelia Steinhauer, Jens Vilstrup Johansen, Kristian Helin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19b38e126b7646daadcd6a9127e78f5d
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spelling	oai:doaj.org-article:19b38e126b7646daadcd6a9127e78f5d2021-11-18T08:26:56ZA screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.1932-620310.1371/journal.pone.0091034https://doaj.org/article/19b38e126b7646daadcd6a9127e78f5d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24651706/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Oncogene-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.Susanne Marije KooistraLise Christine Rudkjær NørgaardMichael James LeesCornelia SteinhauerJens Vilstrup JohansenKristian HelinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91034 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susanne Marije Kooistra Lise Christine Rudkjær Nørgaard Michael James Lees Cornelia Steinhauer Jens Vilstrup Johansen Kristian Helin A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
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.
format	article
author	Susanne Marije Kooistra Lise Christine Rudkjær Nørgaard Michael James Lees Cornelia Steinhauer Jens Vilstrup Johansen Kristian Helin
author_facet	Susanne Marije Kooistra Lise Christine Rudkjær Nørgaard Michael James Lees Cornelia Steinhauer Jens Vilstrup Johansen Kristian Helin
author_sort	Susanne Marije Kooistra
title	A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
title_short	A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
title_full	A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
title_fullStr	A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
title_full_unstemmed	A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.
title_sort	screen identifies the oncogenic micro-rna mir-378a-5p as a negative regulator of oncogene-induced senescence.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/19b38e126b7646daadcd6a9127e78f5d
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A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence.

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