miR-24 triggers epidermal differentiation by controlling actin adhesion and cell migration

Amelio, Ivano; Lena, Anna Maria; Viticchi�, Giuditta; Shalom-Feuerstein, Ruby; Terrinoni, Alessandro; Dinsdale, David; Russo, Giandomenico; Fortunato, Claudia; Bonanno, Elena; Spagnoli, Luigi Giusto; Aberdam, Daniel; Knight, Richard Austen; Candi, Eleonora; Melino, Gerry

Abstract

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.

Citation

Amelio, I., Lena, A. M., Viticchiè, G., Shalom-Feuerstein, R., Terrinoni, A., Dinsdale, D., Russo, G., Fortunato, C., Bonanno, E., Spagnoli, L. G., Aberdam, D., Knight, R. A., Candi, E., & Melino, G. (2012). miR-24 triggers epidermal differentiation by controlling actin adhesion and cell migration. Journal of Cell Biology, 199(2), 347-363. https://doi.org/10.1083/jcb.201203134

• Journal Article Type: Article
• Acceptance Date: Sep 5, 2012
• Online Publication Date: Oct 15, 2012
• Publication Date: Oct 15, 2012
• Deposit Date: Apr 1, 2020
• Journal: The Journal of Cell Biology
• Print ISSN: 1540-8140
• Electronic ISSN: 0021-9525
• Publisher: Rockefeller University Press
• Peer Reviewed: Peer Reviewed
• Volume: 199
• Issue: 2
• Pages: 347-363
• DOI: https://doi.org/10.1083/jcb.201203134
• Keywords: Cell Biology
• Public URL: https://nottingham-repository.worktribe.com/output/4237389
• Publisher URL: https://rupress.org/jcb/article/199/2/347/37053/miR24-triggers-epidermal-differentiation-by