Toll Abelló, AgustínSalgado, RocíoEspinet Solà, BlancaDíaz-Lagares, AngelHernández-Ruiz, EugeniaAndrades, EvelynSandoval, JuanEsteller, ManelPujol Vallverdú, Ramon MariaHernández-Muñoz, Inmaculada2017-01-092017-01-092016Toll 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-z1476-4598http://hdl.handle.net/10230/27852BACKGROUND: 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.application/pdfengThis 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.Pell -- CàncerPell -- Malaltiesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s12943-016-0537-zinfo:eu-repo/semantics/openAccess