The miR-17 family links p63 protein to MAPK signaling to promote the onset of human keratinocyte differentiation.
PLoS One
; 7(9): e45761, 2012.
Article
en En
| MEDLINE
| ID: mdl-23029228
ABSTRACT
The p63 protein plays a key role in regulating human keratinocyte proliferation and differentiation. Although some p63-regulating microRNAs (miRNAs) have been identified in the control of epidermal homeostasis, little is known about miRNAs acting downstream of p63. In this paper, we characterized multiple p63-regulated miRNAs (miR-17, miR-20b, miR-30a, miR-106a, miR-143 and miR-455-3p) and elucidated their roles in the onset of keratinocyte differentiation. We identified RB, p21 and multiple MAPKs as targets of these p63-controlled miRNAs. Upon inhibition of most of these miRNAs, we observed defects in commitment to differentiation that could be reversed by siRNA-mediated silencing of their targets. Furthermore, knockdown of MAPK8 and MAPK9 efficiently restored expression of the early differentiation markers keratin 1 and keratin 10 in p63-silenced primary human keratinocytes. These results highlight new mechanistic roles of multiple miRNAs, particularly the miR-17 family (miR-17, miR-20b and miR-106a), as regulatory intermediates for coordinating p63 with MAPK signaling in the commitment of human mature keratinocytes to early differentiation.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Queratinocitos
/
Diferenciación Celular
/
Sistema de Señalización de MAP Quinasas
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Proteínas Supresoras de Tumor
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MicroARNs
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Interferencia de ARN
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article