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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
08:40

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Published on: April 6, 2012

Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway

María J Bueno1, Marta Gómez de Cedrón, Gonzalo Gómez-López

  • 1Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.

Blood
|April 12, 2011
PubMed

Insights

Multiple microRNAs (miRNAs) coordinately regulate oncogenes like Myc in lymphomas. Down-regulation of these miRNAs enhances Myc activity, driving tumor development and suggesting an imbalance between Myc and miRNA activity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Mammalian genes are often targeted by multiple microRNAs (miRNAs).
  • The extent of coordinated miRNA regulation on single genes remains unclear.
  • Oncogenes like Myc are frequently dysregulated in lymphomas.

Purpose of the Study:

  • To investigate the coordinated regulation of genes by down-regulated miRNAs.
  • To identify specific miRNAs targeting the oncogene Myc in lymphomas.
  • To explore the relationship between Myc activity and miRNA regulation in cancer.

Main Methods:

  • Mapping interactions between down-regulated miRNAs and overexpressed genes in murine and human lymphomas.
  • Utilizing cellular and reporter assays to confirm miRNA regulation of Myc.
  • Analyzing genetic interactions in mouse lymphomas and human Burkitt lymphoma.

Main Results:

  • Myc was identified as a key oncogene with numerous interactions with down-regulated miRNAs in mouse lymphomas.
  • Several miRNAs were confirmed to regulate Myc expression.
  • MYC and its targets were preferentially targeted by down-regulated miRNAs in human Burkitt lymphoma.

Conclusions:

  • Coordinated down-regulation of multiple miRNAs is necessary to enhance critical oncogenes such as Myc.
  • Myc-targeting miRNAs can be repressed by Myc itself.
  • Tumorigenesis may result from an imbalance between Myc oncogene activity and miRNA regulation.

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