TET2 Negatively Regulates Nestin Expression in Human Melanoma

Autor(es):Mostrar menos -

Gomes, Camilla B. F. ^{[1, 2]} ; Zechin, Karina G. ^[2] ; Xu, Shuyun ^[1] ; Stelini, Rafael F. ^[3] ; Nishimoto, Ines N. ^[4] ; Zhan, Qian ^[1] ; Xu, Ting ^[1] ; Qin, Gungwei ^[1] ; Treister, Nathaniel S. ^[5] ; Murphy, George F. ^[1] ; Lian, Christine G. ^[1]

Afiliação do(s) autor(es)

^[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Program Dennatopathol, Dept Pathol, 221 Longwood Ave, EBRC Ste 401, Boston, MA 02115 - USA

^[2] Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Program Oral Pathol, Piracicaba - Brazil

^[3] Univ Estadual Campinas, Sch Med Sci, Dept Pathol, Piracicaba - Brazil

^[4] AC Camargo Canc Ctr, Dept Head & Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[5] Harvard Univ, Brigham & Womens Hosp, Sch Dent Med, Div Oral Med & Dent, Boston, MA 02115 - USA

• Tipo de documento: Artigo Científico
• Fonte: American Journal of Pathology; v. 186, n. 6, p. 1427-1434, JUN 2016.
• Citações Web of Science: 2

Resumo

Although melanoma is an aggressive cancer, the understanding of the virulence-conferring pathways involved remains incomplete. We have demonstrated that Loss of ten-eleven translocation methyl cytosine dioxygenase (TET2)-mediated 5-hydroxymethylcytosine (5-hmC) is an epigenetic driver of melanoma growth and a biomarker of clinical virulence. We also have determined that the intermediate filament protein nestin correlates with tumorigenic and invasive melanoma growth. Here we examine the relationships between these two biomarkers. Immunohistochemistry staining of nestin and 5-hmC in 53 clinically annotated primary and metastatic patient melanomas revealed a significant negative correlation. Restoration of 5-hmC, as assessed in a human melanoma cell Line by introducing full-length TET2 and TET2-mutated constructs, decreased nestin gene and protein expression in vitro. Genome-wide mapping using hydroxymethylated DNA immunoprecipitation sequencing disclosed significantly less 5-hmC binding in the 3' untranslated region of the nestin gene in melanoma compared to nevi, and 5-hmC binding in this region was significantly increased after TET2 overexpression in human melanoma cells in vitro. Our findings provide evidence suggesting that nestin regulation is negatively controlled epigenetically by TET2 via 5-hmC binding at the 3' untranslated region of the nestin gene, providing one potential pathway for understanding melanoma growth characteristics. Studies are now indicated to further define the interplay between 5-hmC, nestin expression, and melanoma virulence. (AU)

• Processo FAPESP: 12/14008-0 - Correlação entre prognóstico de melanoma maligno humano e expressão da enzima ácido graxo sintase e de proteínas envolvidas no ciclo celular e na angiogênese
• Beneficiário: Camilla Borges Ferreira Gomes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/13834-4 - Correlação entre prognóstico de melanoma maligno humano e expressão da enzima ácido graxo sintase e de proteínas envolvidas no ciclo celular e na angiogênese
• Beneficiário: Karina Gottardello Zecchin
• Modalidade de apoio: Auxílio à Pesquisa - Regular