Extrachromosomal HPV-16 LCR transcriptional activation by HDACi opposed by cellular differentiation and DNA integration
Metrics: PDF 1010 views | HTML 1396 views | ?
Ekaterina Dimitrova Bojilova1, Christine Weyn1, Marie-Hélène Antoine2, Véronique Fontaine1
1Université Libre de Bruxelles (ULB), Faculty of Pharmacy, Unit of Pharmaceutical Microbiology and Hygiene, 1050 Brussels, Belgium
2Université Libre de Bruxelles (ULB) Faculty of Medicine, Laboratory of Experimental Hormonology, 1070 Brussels, Belgium
Véronique Fontaine, email: email@example.com
Keywords: human papillomavirus, histone deacetylase inhibitor, transcription, integration, differentiation
Received: April 07, 2016 Accepted: September 13, 2016 Published: September 26, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.