| First Author | Nagosa S | Year | 2017 |
| Journal | Stem Cell Reports | Volume | 9 |
| Issue | 6 | Pages | 1991-2004 |
| PubMed ID | 29198823 | Mgi Jnum | J:315114 |
| Mgi Id | MGI:6829420 | Doi | 10.1016/j.stemcr.2017.10.030 |
| Citation | Nagosa S, et al. (2017) microRNA-184 Induces a Commitment Switch to Epidermal Differentiation. Stem Cell Reports 9(6):1991-2004 |
| abstractText | 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-184(C57U) 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. |
