Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21Waf1/Cip1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-04

AUTHORS

V Borgdorff, M E Lleonart, C L Bishop, D Fessart, A H Bergin, M G Overhoff, D H Beach

ABSTRACT

Overexpression of Ras(G12V) in primary cells induces a permanent growth arrest called oncogene-induced senescence (OIS) that serves as a fail-safe mechanism against malignant transformation. We have performed a genome-wide small interfering RNA (siRNA) screen and a microRNA (miRNA) screen to identify mediators of OIS and show that siRNA-mediated knockdown of p21(Waf1/Cip1) rescues from Ras(G12V)-induced senescence in human mammary epithelial cells (HMECs). Moreover, we isolated a total of 28 miRNAs that prevented Ras(G12V)-induced growth arrest, among which all of the miR-106b family members were present. In addition, we obtained a number of hits, miR-130b, miR-302a, miR-302b, miR302c, miR-302d, miR-512-3p and miR-515-3p with seed sequences very similar to miR-106b family members. We show that overexpression of all these miRNAs rescues HMECs from Ras(G12V)-induced senescence by prevention of Ras(G12V)-induced upregulation of p21(Waf1/Cip1). Our results establish an important role for the cell cycle inhibitor p21(Waf1/Cip1) in growth control of HMECs and extend the repertoire of miRNAs that modulate the activity of this tumour suppressor. More... »

PAGES

2262

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2009.497

DOI

http://dx.doi.org/10.1038/onc.2009.497

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043109272

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20101223


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