A combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancer

Cancer Res. 2012 Jan 1;72(1):154-64. doi: 10.1158/0008-5472.CAN-11-2484. Epub 2011 Nov 4.

Abstract

Oncomirs are microRNAs (miRNA) that acts as oncogenes or tumor suppressor genes. Efficient identification of oncomirs remains a challenge. Here we report a novel, clinically guided genetic screening approach for the identification of oncomirs, identifying mir-30d through this strategy. mir-30d regulates tumor cell proliferation, apoptosis, senescence, and migration. The chromosomal locus harboring mir-30d was amplified in more than 30% of multiple types of human solid tumors (n = 1,283). Importantly, higher levels of mir-30d expression were associated significantly with poor clinical outcomes in ovarian cancer patients (n = 330, P = 0.0016). Mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase CASP3. The guided genetic screening approach validated by this study offers a powerful tool to identify oncomirs that may have utility as biomarkers or targets for drug development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation
  • Chromosome Mapping
  • Comparative Genomic Hybridization*
  • Female
  • Humans
  • In Situ Hybridization
  • Mice
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Real-Time Polymerase Chain Reaction

Substances

  • MIRN30b microRNA, human
  • MicroRNAs