Prediction and preliminary validation of oncogene regulation by miRNAs

BMC Mol Biol. 2007 Sep 18;8:79. doi: 10.1186/1471-2199-8-79.

Abstract

Background: MicroRNAs (miRNAs) are one of the most abundant groups of regulatory genes in multicellular organisms, playing important roles in many fundamental cellular processes. More than four hundred miRNAs have been identified in humans and the deregulation of miRNA expression has been also shown in many cancers. Despite the postulated involvement of miRNAs in tumourigenesis, there are only a few examples where an oncogene or a tumour suppressor has been identified as a miRNA target.

Results: Here, we present an in silico analysis of potential miRNA- oncogene interactions. Moreover, we have tested the validity of two possible interactions of miRNAs with genes related to cancer. We present evidence for the down-regulation of c-MYC, one of the most potent and frequently deregulated oncogenes, by let-7 miRNA, via the predicted binding site in the 3'UTR, and verify the suppression of BCL-2 by miR16.

Conclusion: In this work both bioinformatic and experimental approaches for the prediction and validation of possible targets for miRNAs have been used. A list of putative targets for different oncomirs, validation of which would be of special interest, is proposed and two such interactions have been experimentally validated.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Cloning, Molecular / methods
  • Computational Biology / methods
  • Databases, Genetic
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Targeting / methods*
  • Genes, Tumor Suppressor / drug effects
  • Genes, bcl-2 / drug effects
  • Genes, bcl-2 / genetics
  • Genes, myc / drug effects
  • Genes, myc / genetics
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / pharmacology
  • Models, Genetic
  • Molecular Sequence Data
  • Oncogenes / drug effects
  • Oncogenes / genetics*
  • Predictive Value of Tests
  • RNA Interference*
  • Sequence Analysis, RNA / methods

Substances

  • 3' Untranslated Regions
  • MicroRNAs