miR-181a decelerates proliferation in cutaneous squamous cell carcinoma by targeting the proto-oncogene KRAS.

Détails

Ressource 1Télécharger: journal.pone.0185028.pdf (2376.66 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_29F7F9833953
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
miR-181a decelerates proliferation in cutaneous squamous cell carcinoma by targeting the proto-oncogene KRAS.
Périodique
PLoS One
Auteur(s)
Neu J., Dziunycz P.J., Dzung A., Lefort K., Falke M., Denzler R., Freiberger S.N., Iotzova-Weiss G., Kuzmanov A., Levesque M.P., Dotto G.P., Hofbauer GFL
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
12
Numéro
9
Pages
e0185028
Langue
anglais
Résumé
Cutaneous squamous cell carcinoma (SCC) is the second most common human skin cancer with a rapidly increasing incidence among the Caucasian population. Among the many regulators, responsible for cancer progression and growth, microRNAs (miRNA) are generally accepted as key players by now. In our current study we found that microRNA-181a (miR-181a) shows low abundance in SCC compared to normal epidermal skin. In vitro, miRNA downregulation in normal primary keratinocytes induced increased proliferation, while in vivo miR-181a downregulation in HaCaT normal keratinocytes showed tumor-like growth increase up to 50%. Inversely, upregulation of these miRNAs in cancer cells lead to reduced cellular proliferation and induction of apoptosis in vitro. An in vivo therapeutic model with induced miR-181a expression in SCC13 cancer cells reduced tumor formation in mice by 80%. Modulation of miR-181a levels showed an inverse correlation with the proto-oncogene KRAS both on mRNA and protein level by direct interaction. Knockdown of KRAS mimicked the anti-proliferative effects of miR-181a overexpression in patient-derived SCC cells and abolished the enhanced viability of HaCaT cells following miR-181a knockdown. Furthermore, phospho-ERK levels correlated with KRAS levels, suggesting that the observed effects were mediated via the MAPK signaling pathway. miR-181a seemed regulated during keratinocyte differentiation probably in order to amplify the tumor suppressive character of differentiation. Taken together, miR-181a plays a crucial tumor suppressive role in SCC by targeting KRAS and could be a promising candidate for a miRNA based therapy.

Pubmed
Web of science
Open Access
Oui
Création de la notice
16/10/2017 17:47
Dernière modification de la notice
20/08/2019 14:09
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