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

Toll Abelló, Agustín; Salgado, Rocío; Espinet Solà, Blanca; Díaz-Lagares, Angel; Hernández-Ruiz, Eugenia; Andrades, Evelyn; Sandoval, Juan; Esteller, Manel; Pujol Vallverdú, Ramon Maria; Hernández-Muñoz, Inmaculada

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

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dc.contributor.author Toll Abelló, Agustínca
dc.contributor.author Salgado, Rocíoca
dc.contributor.author Espinet Solà, Blancaca
dc.contributor.author Díaz-Lagares, Angelca
dc.contributor.author Hernández-Ruiz, Eugeniaca
dc.contributor.author Andrades, Evelynca
dc.contributor.author Sandoval, Juanca
dc.contributor.author Esteller, Manelca
dc.contributor.author Pujol Vallverdú, Ramon Mariaca
dc.contributor.author Hernández-Muñoz, Inmaculadaca
dc.date.accessioned 2017-01-09T09:08:19Z
dc.date.available 2017-01-09T09:08:19Z
dc.date.issued 2016
dc.description.abstract BACKGROUND: 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.ca
dc.description.sponsorship This study was supported by grants PI15/00236, PI041728, PI10/00785, FIS PI11/02070, RD09/0076/00036, RD06/0020/0040, and PS09/00973 from Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III FEDER, SAF2010- 16089, Ministerio de Economía y Competitividad, Spain, from the “Xarxa de Bancs de tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC)”. IHM is an investigator at the Miguel Servet program (Instituto de Salud Carlos III). ADL is funded by the ISCIII through a research contract Río Hortega (CM14/ 00067). ME is an ICREA Research Professor.
dc.format.mimetype application/pdfca
dc.identifier.citation Toll A, Salgado R, Espinet B, Díaz-Lagares A, Hernández-Ruiz E, Andrades E. et al. MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression. Mol Cancer. 2016 Jul 25;15(1):53. doi: 10.1186/s12943-016-0537-zca
dc.identifier.doi http://dx.doi.org/10.1186/s12943-016-0537-z
dc.identifier.issn 1476-4598
dc.identifier.uri http://hdl.handle.net/10230/27852
dc.language.iso engca
dc.publisher BioMed Centralca
dc.relation.ispartof Molecular Cancer. 2016 Jul 25;15(1):53
dc.rights This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ca
dc.subject.other Pell -- Càncerca
dc.subject.other Pell -- Malaltiesca
dc.title MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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