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

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 b...

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Autores: Toll Abelló, Agustí, Salgado, Rocío, Espinet Solà, Blanca, Diaz-Lagares, Angel, Hernández Ruiz, Eugenia, Andrades, Evelyn, Sandoval, Juan, Esteller, Manel, 1968-, Pujol, Ramon M., Hernández Muñoz, Inmaculada
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126536
Acceso en línea:https://hdl.handle.net/2445/126536
Access Level:acceso abierto
Palabra clave:Epigenètica
Càncer de pell
Ceratosi
Epigenetics
Skin cancer
Keratosis
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spelling MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progressionToll Abelló, AgustíSalgado, RocíoEspinet Solà, BlancaDiaz-Lagares, AngelHernández Ruiz, EugeniaAndrades, EvelynSandoval, JuanEsteller, Manel, 1968-Pujol, Ramon M.Hernández Muñoz, InmaculadaEpigenèticaCàncer de pellCeratosiEpigeneticsSkin cancerKeratosisBackground: 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.BioMed Central2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/126536Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12943-016-0537-zMolecular Cancer, 2016, vol. 15, num. 1, p. 53https://doi.org/10.1186/s12943-016-0537-zcc-by (c) Toll, Agustí et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1265362026-05-27T06:46:51Z
dc.title.none.fl_str_mv MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
title MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
spellingShingle MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
Toll Abelló, Agustí
Epigenètica
Càncer de pell
Ceratosi
Epigenetics
Skin cancer
Keratosis
title_short MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
title_full MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
title_fullStr MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
title_full_unstemmed MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
title_sort MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression
dc.creator.none.fl_str_mv Toll Abelló, Agustí
Salgado, Rocío
Espinet Solà, Blanca
Diaz-Lagares, Angel
Hernández Ruiz, Eugenia
Andrades, Evelyn
Sandoval, Juan
Esteller, Manel, 1968-
Pujol, Ramon M.
Hernández Muñoz, Inmaculada
author Toll Abelló, Agustí
author_facet Toll Abelló, Agustí
Salgado, Rocío
Espinet Solà, Blanca
Diaz-Lagares, Angel
Hernández Ruiz, Eugenia
Andrades, Evelyn
Sandoval, Juan
Esteller, Manel, 1968-
Pujol, Ramon M.
Hernández Muñoz, Inmaculada
author_role author
author2 Salgado, Rocío
Espinet Solà, Blanca
Diaz-Lagares, Angel
Hernández Ruiz, Eugenia
Andrades, Evelyn
Sandoval, Juan
Esteller, Manel, 1968-
Pujol, Ramon M.
Hernández Muñoz, Inmaculada
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigenètica
Càncer de pell
Ceratosi
Epigenetics
Skin cancer
Keratosis
topic Epigenètica
Càncer de pell
Ceratosi
Epigenetics
Skin cancer
Keratosis
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126536
url https://hdl.handle.net/2445/126536
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12943-016-0537-z
Molecular Cancer, 2016, vol. 15, num. 1, p. 53
https://doi.org/10.1186/s12943-016-0537-z
dc.rights.none.fl_str_mv cc-by (c) Toll, Agustí et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Toll, Agustí et al., 2016
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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