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

Overview

MeSH Major

  • Genes, myc
  • Lymphoma, B-Cell
  • MicroRNAs

abstract

  • The miR-17 approximately 92 cluster is frequently amplified or overexpressed in human cancers and has emerged as the prototypical oncogenic polycistron microRNA (miRNA). miR-17 approximately 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 approximately 92, we show here that sustained expression of endogenous miR-17 approximately 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 approximately 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.

publication date

  • December 15, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2800095

Digital Object Identifier (DOI)

  • 10.1101/gad.1872909

PubMed ID

  • 20008931

Additional Document Info

start page

  • 2806

end page

  • 11

volume

  • 23

number

  • 24