miR-19 is a key oncogenic component of mir-17-92

Olive, V., Bennett, M. J., Walker, J. C., Ma, C., Jiang, I., Cordon-Cardo, C., Li, Q. J., Lowe, S. W., Hannon, G. J., He, L. (December 2009) miR-19 is a key oncogenic component of mir-17-92. Genes & Development, 23 (24). pp. 2839-2849. ISSN 0890-9369

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URL: http://www.ncbi.nlm.nih.gov/pubmed/20008935
DOI: 10.1101/gad.1861409

Abstract

Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, where one primary transcript yields six individual miRNAs. Here, we functionally dissected the individual components of mir-17-92 by assaying their tumorigenic potential in vivo. Using the E mu-myc model of mouse B-cell lymphoma, we identified miR-19 as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. The oncogenic activity of miR-19 is at least in part due to its repression of the tumor suppressor Pten. Consistently, miR-19 activates the Akt-mTOR (mammalian target of rapamycin) pathway, thereby functionally antagonizing Pten to promote cell survival. Our findings reveal the essential role of miR-19 in mediating the oncogenic activity of mir-17-92, and implicate the functional diversity of mir-17-92 components as the molecular basis for its pleiotropic effects during tumorigenesis.

Item Type: Paper
Uncontrolled Keywords: Cancer apoptosis c myc microRNAs mir 17 92 mir 19 LET 7 MICRORNA FAMILY Let 7 microrna family B CELL LYMPHOMA b cell lymphoma TUMOR SUPPRESSION tumor suppression MALIGNANT LYMPHOMA malignant lymphoma SMALL RNAS small rnas PTEN pten MYC myc EXPRESSION expression CLUSTER cluster TUMORIGENESIS tumorigenesis
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
diseases & disorders > cancer > cancer types > lymphoma
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Lowe lab
CSHL Cancer Center Shared Resources > Animal Services
Depositing User: Editor Margaret Fantz
Date: 15 December 2009
Date Deposited: 16 Apr 2012 18:18
Last Modified: 29 Dec 2014 20:01
PMCID: PMC2800084
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26135

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