microRNA-184 Induces a Commitment Switch to Epidermal Differentiation

Stem Cell Reports. 2017 Dec 12;9(6):1991-2004. doi: 10.1016/j.stemcr.2017.10.030. Epub 2017 Nov 30.


miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced clonogenicity and accelerated differentiation of human epidermal cells. We showed that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch activation and epidermal differentiation. The disease-causing miR-184C57U mutant failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss-of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1, miR-184 regulates the transition from proliferation to early differentiation, while mis-expression or mutation in miR-184 results in impaired homeostasis.

Keywords: FIH1; K15; cornea; epidermis; hair follicle; miR-184; miRNA-184; microRNA; notch; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blindness / genetics*
  • Blindness / pathology
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Epidermis / growth & development*
  • Epidermis / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Keratin-15 / genetics
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • Mixed Function Oxygenases / genetics
  • Phosphoproteins / genetics
  • Receptors, Notch / genetics
  • Signal Transduction / genetics
  • Stem Cells / metabolism
  • Trans-Activators / genetics


  • Keratin-15
  • MIRN184 microRNA, mouse
  • MicroRNAs
  • Phosphoproteins
  • Receptors, Notch
  • Trans-Activators
  • Trp63 protein, mouse
  • Mixed Function Oxygenases
  • factor inhibiting hypoxia-inducible factor 1, mouse