Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers

Cancer Cell. 2017 Apr 10;31(4):576-590.e8. doi: 10.1016/j.ccell.2017.03.004.


Cyclins and cyclin-dependent kinases (CDKs) are hyperactivated in numerous human tumors. To identify means of interfering with cyclins/CDKs, we performed nine genome-wide screens for human microRNAs (miRNAs) directly regulating cell-cycle proteins. We uncovered a distinct class of miRNAs that target nearly all cyclins/CDKs, which are very effective in inhibiting cancer cell proliferation. By profiling the response of over 120 human cancer cell lines, we derived an expression-based algorithm that can predict the response of tumors to cell-cycle-targeting miRNAs. Using systemic administration of nanoparticle-formulated miRNAs, we inhibited tumor progression in seven mouse xenograft models, including three treatment-refractory patient-derived tumors, without affecting normal tissues. Our results highlight the utility of using cell-cycle-targeting miRNAs for treatment of refractory cancer types.

Keywords: cancers; cell cycle; cyclin-dependent kinases; cyclins; microRNAs.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Algorithms
  • Animals
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genome-Wide Association Study
  • Humans
  • Mice, Inbred Strains
  • MicroRNAs / administration & dosage
  • MicroRNAs / genetics*
  • MicroRNAs / pharmacology
  • Mutation
  • Nanoparticles
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Xenograft Model Antitumor Assays


  • 3' Untranslated Regions
  • Antineoplastic Agents
  • KRAS protein, human
  • MIRN193 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins p21(ras)