miR-24 triggers epidermal differentiation by controlling actin adhesion and cell migration.
During keratinocyte differentiation and stratification, cells undergo extensive remodeling of their actin cytoskeleton, which is important to control cell mobility and to coordinate and stabilize adhesive structures necessary for functional epithelia. Limited knowledge exists on how the actin cytoskeleton is remodeled in epithelial stratification and whether cell shape is a key determinant to trigger terminal differentiation. In this paper, using human keratinocytes and mouse epidermis as models, we implicate miR-24 in actin adhesion dynamics and demonstrate that miR-24 directly controls actin cable formation and cell mobility. miR-24 overexpression in proliferating cells was sufficient to trigger keratinocyte differentiation both in vitro and in vivo and directly repressed cytoskeletal modulators (PAK4, Tks5, and ArhGAP19). Silencing of these targets recapitulated the effects of miR-24 overexpression. Our results uncover a new regulatory pathway involving a differentiation-promoting microribonucleic acid that regulates actin adhesion dynamics in human and mouse epidermis.
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Ivano
I
Amelio
Anna Maria
AM
Lena
Giuditta
G
Viticchiè
Ruby
R
Shalom-Feuerstein
Alessandro
A
Terrinoni
David
D
Dinsdale
Giandomenico
G
Russo
Claudia
C
Fortunato
Elena
E
Bonanno
Luigi Giusto
LG
Spagnoli
Daniel
D
Aberdam
Richard Austen
RA
Knight
Eleonora
E
Candi
Gerry
G
Melino
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins; D034622:RNA Interference; D034741:RNA, Small Interfering; D054462:p21-Activated Kinases
C521098:ARHGAP19 protein, human; C114235:Fish protein, mouse; D020690:GTPase-Activating Proteins; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C492065:Pak4 protein, mouse; D054462:p21-Activated Kinases