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MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression.


ABSTRACT: 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.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.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.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.

SUBMITTER: Toll A 

PROVIDER: S-EPMC4960761 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression.

Toll Agustí A   Salgado Rocío R   Espinet Blanca B   Díaz-Lagares Angel A   Hernández-Ruiz Eugenia E   Andrades Evelyn E   Sandoval Juan J   Esteller Manel M   Pujol Ramón M RM   Hernández-Muñoz Inmaculada I  

Molecular cancer 20160725 1


<h4>Background</h4>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.<h4>Methods</h4>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 treatme  ...[more]

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