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A genome-scale screen reveals context-dependent ovarian cancer sensitivity to miRNA overexpression.

Molecular systems biology | 2015

Large-scale molecular annotation of epithelial ovarian cancer (EOC) indicates remarkable heterogeneity in the etiology of that disease. This diversity presents a significant obstacle against intervention target discovery. However, inactivation of miRNA biogenesis is commonly associated with advanced disease. Thus, restoration of miRNA activity may represent a common vulnerability among diverse EOC oncogenotypes. To test this, we employed genome-scale, gain-of-function, miRNA mimic toxicity screens in a large, diverse spectrum of EOC cell lines. We found that all cell lines responded to at least some miRNA mimics, but that the nature of the miRNA mimics provoking a response was highly selective within the panel. These selective toxicity profiles were leveraged to define modes of action and molecular response indicators for miRNA mimics with tumor-suppressive characteristics in vivo. A mechanistic principle emerging from this analysis was sensitivity of EOC to miRNA-mediated release of cell fate specification programs, loss of which may be a prerequisite for development of this disease.

Pubmed ID: 26655797 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R35 CA197717
  • Agency: NCI NIH HHS, United States
    Id: U54 CA151668
  • Agency: NCI NIH HHS, United States
    Id: U54CA151668
  • Agency: NCI NIH HHS, United States
    Id: R01 CA129451
  • Agency: NIGMS NIH HHS, United States
    Id: T32-GM008203
  • Agency: NCI NIH HHS, United States
    Id: R01 CA071443
  • Agency: NCI NIH HHS, United States
    Id: CA71443
  • Agency: NCI NIH HHS, United States
    Id: P50CA083639
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008203
  • Agency: NCI NIH HHS, United States
    Id: P50 CA083639
  • Agency: NCI NIH HHS, United States
    Id: CA129451

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