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Pàgina inicial > Articles > Articles publicats > MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression |
Data: | 2016 |
Resum: | 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. The online version of this article (doi:10. 1186/s12943-016-0537-z) contains supplementary material, which is available to authorized users. |
Ajuts: | Instituto de Salud Carlos III PI15-00236 Instituto de Salud Carlos III PI041728 Instituto de Salud Carlos III PI10-00785 Instituto de Salud Carlos III PI11-02070 Instituto de Salud Carlos III FEDER/RD09-0076-00036 Instituto de Salud Carlos III FEDER/RD06-0020-0040 Instituto de Salud Carlos III PS09-00973 Ministerio de Economía y Competitividad SAF2010-16089 Instituto de Salud Carlos III CM14-00067 |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | MiR-204 ; Cutaneous squamous cell carcinoma ; Actinic keratosis ; Sun-induced keratinocyte intraepithelial neoplasia ; DNA methylation ; MAPK ; STAT3 |
Publicat a: | Molecular cancer, Vol. 15 (july 2016) , ISSN 1476-4598 |
15 p, 2.0 MB |