Genetic dissection of the miR-17-92 cluster of microRNAs in Myc-induced B-cell lymphomas Journal Article

   

Authors:	Mu, P.; Han, Y. C.; Betel, D.; Yao, E.; Squatrito, M.; Ogrodowski, P.; de Stanchina, E.; D'Andrea, A.; Sander, C.; Ventura, A.
Article Title:	Genetic dissection of the miR-17-92 cluster of microRNAs in Myc-induced B-cell lymphomas
Abstract:	The miR-17-92 cluster is frequently amplified or over-expressed in human cancers and has emerged as the prototypical oncogenic polycistron microRNA (miRNA). miR-17-92 is a direct transcriptional target of c-Myc, and experiments in a mouse model of B-cell lymphomas have shown cooperation between these two oncogenes. However, both the molecular mechanism underlying this cooperation and the individual miRNAs that are responsible for it are unknown. By using a conditional knockout allele of miR-17-92, we show here that sustained expression of endogenous miR-17-92 is required to suppress apoptosis in Myc-driven B-cell lymphomas. Furthermore, we show that among the six miRNAs that are encoded by miR-17-92, miR-19a and miR-19b are absolutely required and largely sufficient to recapitulate the oncogenic properties of the entire cluster. Finally, by combining computational target prediction, gene expression profiling, and an in vitro screening strategy, we identify a subset of miR-19 targets that mediate its prosurvival activity. © 2009 by Cold Spring Harbor Laboratory Press.
Keywords:	controlled study; gene cluster; gene deletion; nonhuman; animal cell; mouse; animals; mice; allele; cell survival; gene targeting; apoptosis; microrna; gene expression profiling; animal experiment; animal model; in vitro study; cell line, tumor; prediction; mice, inbred c57bl; b cell lymphoma; lymphoma, b-cell; mice, nude; genes, myc; carcinogenicity; micrornas; oncogene c myc; mir-17-92; myc; knockout gene; stable expression
Journal Title:	Genes and Development
Volume:	23
Issue:	24
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Date Published:	2009-12-15
Start Page:	2806
End Page:	2811
Language:	English
DOI:	10.1101/gad.1872909
PUBMED:	20008931
PROVIDER:	scopus
PMCID:	PMC2800095
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-72849125619&partnerID=40&md5=53c7f08d9a03eabb29811d5bf419458c
Notes:	--- - "Cited By (since 1996): 20" - "Export Date: 30 November 2010" - "CODEN: GEDEE" - "Source: Scopus"

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