Unknown

Dataset Information

0

MicroRNA-184 Induces a Commitment Switch to Epidermal Differentiation.


ABSTRACT: 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.

SUBMITTER: Nagosa S 

PROVIDER: S-EPMC5785777 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 epi  ...[more]

Similar Datasets

| S-EPMC5239556 | biostudies-literature
| S-EPMC2587229 | biostudies-literature
| S-EPMC6591972 | biostudies-literature
| S-EPMC4396470 | biostudies-literature
| S-EPMC3227627 | biostudies-literature
| S-EPMC6291208 | biostudies-literature
| S-EPMC4691128 | biostudies-literature
| S-EPMC3631964 | biostudies-literature
| S-EPMC3277884 | biostudies-literature
| S-EPMC4387599 | biostudies-other