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Title: MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
Author: Toll Abelló, Agustí
Salgado, Rocío
Espinet Solà, Blanca
Diaz-Lagares, Angel
Hernández Ruiz, Eugenia
Andrades, Evelyn
Sandoval, Juan
Esteller, Manel
Pujol, Ramon M.
Hernández Muñoz, Inmaculada
Keywords: Epigenètica
Càncer de pell
Skin cancer
Issue Date: 25-Jul-2016
Publisher: BioMed Central
Abstract: Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and frequently progresses from an actinic keratosis (AK), a sun-induced keratinocyte intraepithelial neoplasia (KIN). Epigenetic mechanisms involved in the phenomenon of progression from AK to cSCC remain to be elicited. Methods: Expression of microRNAs in sun-exposed skin, AK and cSCC was analysed by Agilent microarrays. DNA methylation of miR-204 promoter was determined by bisulphite treatment and pyrosequencing. Identification of miR-204 targets and pathways was accomplished in HaCat cells. Immunofluorescence and immunohistochemistry were used to analyze STAT3 activation and PTPN11 expression in human biopsies. Results: cSCCs display a marked downregulation of miR-204 expression when compared to AK. DNA methylation of miR-204 promoter was identified as one of the repressive mechanisms that accounts for miR-204 silencing in cSCC. In HaCaT cells miR-204 inhibits STAT3 and favours the MAPK signaling pathway, likely acting through PTPN11, a nuclear tyrosine phosphatase that is a direct miR-204 target. In non-peritumoral AK lesions, activated STAT3, as detected by pY705-STAT3 immunofluorescence, is retained in the membrane and cytoplasm compartments, whereas AK lesions adjacent to cSCCs display activated STAT3 in the nuclei. Conclusions: Our data suggest that miR-204 may act as a 'rheostat' that controls the signalling towards the MAPK pathway or the STAT3 pathway in the progression from AK to cSCC.
Note: Reproducció del document publicat a:
It is part of: Molecular Cancer, 2016, vol. 15, num. 1, p. 53
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ISSN: 1476-4598
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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