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Extrachromosomal HPV-16 LCR transcriptional activation by HDACi opposed by cellular differentiation and DNA integration.
Bojilova, Ekaterina Dimitrova; Weyn, Christine; Antoine, Marie-Hélène; Fontaine, Véronique.
Afiliação
  • Bojilova ED; Université Libre de Bruxelles (ULB), Faculty of Pharmacy, Unit of Pharmaceutical Microbiology and Hygiene, 1050 Brussels, Belgium.
  • Weyn C; Université Libre de Bruxelles (ULB), Faculty of Pharmacy, Unit of Pharmaceutical Microbiology and Hygiene, 1050 Brussels, Belgium.
  • Antoine MH; Université Libre de Bruxelles (ULB) Faculty of Medicine, Laboratory of Experimental Hormonology, 1070 Brussels, Belgium.
  • Fontaine V; Université Libre de Bruxelles (ULB), Faculty of Pharmacy, Unit of Pharmaceutical Microbiology and Hygiene, 1050 Brussels, Belgium.
Oncotarget ; 7(46): 75526-75538, 2016 Nov 15.
Article em En | MEDLINE | ID: mdl-27705914
Histone deacetylase inhibitors (HDACi) have been shown to render HPV-carrying cells susceptible to intrinsic and extrinsic apoptotic signals. As such, these epigenetic drugs have entered clinical trials in the effort to treat cervical cancer. Here, we studied the effect of common HDACi, with an emphasis on Trichostatin A (TSA), on the transcriptional activity of the HPV-16 Long Control Region (LCR) in order to better understand the impact of these agents in the context of the HPV life cycle and infection. HDACi strongly induced transcription of the firefly luciferase reporter gene under the control of the HPV-16 LCR in a variety of cell lines. In the HaCaT keratinocyte cell line undergoing differentiation induced by TSA, we observed a reduction in LCR-controlled transcription. Three major AP-1 binding sites in the HPV-16 LCR are involved in the regulation by TSA. However, whatever the status of differentiation of the HaCaT cells, TSA induced integration of extra-chromosomal transfected DNA into the cellular genome. Although these data suggest caution using HDACi in the treatment of HR HPV infection, further in vivo studies are necessary to better assess the risk.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação Viral da Expressão Gênica / Ativação Transcricional / Integração Viral / Infecções por Papillomavirus / Papillomavirus Humano 16 / Inibidores de Histona Desacetilases Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação Viral da Expressão Gênica / Ativação Transcricional / Integração Viral / Infecções por Papillomavirus / Papillomavirus Humano 16 / Inibidores de Histona Desacetilases Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article