Cargando…
Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer
BACKGROUND: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negat...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084374/ https://www.ncbi.nlm.nih.gov/pubmed/27793210 http://dx.doi.org/10.1186/s40463-016-0168-9 |
_version_ | 1782463367909212160 |
---|---|
author | Idris, Sherif Lindsay, Cameron Kostiuk, Morris Andrews, Colin Côté, David W. J. O’Connell, Daniel A. Harris, Jeffrey Seikaly, Hadi Biron, Vincent L. |
author_facet | Idris, Sherif Lindsay, Cameron Kostiuk, Morris Andrews, Colin Côté, David W. J. O’Connell, Daniel A. Harris, Jeffrey Seikaly, Hadi Biron, Vincent L. |
author_sort | Idris, Sherif |
collection | PubMed |
description | BACKGROUND: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negative survival outcomes in several human cancers. We aimed to determine the role of EZH2 as a potential therapeutic epigenetic target in HPV-positive and negative OPSCC. METHODS: The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) in 2 HPV-positive and 2 HPV-negative cell lines. The cell lines were then cultured and treated with one of 3 EZH2 epigenetic inhibitors (3-deazaneplanocin A, GSK-343 and EPZ005687) or DMSO (control). Following 2, 4 and 7 days of treatment, cells were analyzed and compared by gene expression, cell survival and proliferation assays. RESULTS: EZH2 targeting resulted in greater inhibition of growth and survival in HPV-positive compared to HPV-negative cells lines. The expression profile of genes important in OPSCC also differed according to HPV-positivity for Ki67, CCND1, MET and PTEN/PIK3CA, but remained unchanged for EGFR, CDKN2A and p53. CONCLUSION: Inhibition of EZH2 has anti-tumorigenic effects on OPSCC cells in culture that is more pronounced in HPV-positive cell lines. EZH2 is a promising epigenetic target for the treatment of OPSCC. |
format | Online Article Text |
id | pubmed-5084374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50843742016-10-31 Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer Idris, Sherif Lindsay, Cameron Kostiuk, Morris Andrews, Colin Côté, David W. J. O’Connell, Daniel A. Harris, Jeffrey Seikaly, Hadi Biron, Vincent L. J Otolaryngol Head Neck Surg Original Research Article BACKGROUND: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negative survival outcomes in several human cancers. We aimed to determine the role of EZH2 as a potential therapeutic epigenetic target in HPV-positive and negative OPSCC. METHODS: The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) in 2 HPV-positive and 2 HPV-negative cell lines. The cell lines were then cultured and treated with one of 3 EZH2 epigenetic inhibitors (3-deazaneplanocin A, GSK-343 and EPZ005687) or DMSO (control). Following 2, 4 and 7 days of treatment, cells were analyzed and compared by gene expression, cell survival and proliferation assays. RESULTS: EZH2 targeting resulted in greater inhibition of growth and survival in HPV-positive compared to HPV-negative cells lines. The expression profile of genes important in OPSCC also differed according to HPV-positivity for Ki67, CCND1, MET and PTEN/PIK3CA, but remained unchanged for EGFR, CDKN2A and p53. CONCLUSION: Inhibition of EZH2 has anti-tumorigenic effects on OPSCC cells in culture that is more pronounced in HPV-positive cell lines. EZH2 is a promising epigenetic target for the treatment of OPSCC. BioMed Central 2016-10-28 /pmc/articles/PMC5084374/ /pubmed/27793210 http://dx.doi.org/10.1186/s40463-016-0168-9 Text en © The Author(s). 2016 Open AccessThis 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. |
spellingShingle | Original Research Article Idris, Sherif Lindsay, Cameron Kostiuk, Morris Andrews, Colin Côté, David W. J. O’Connell, Daniel A. Harris, Jeffrey Seikaly, Hadi Biron, Vincent L. Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
title | Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
title_full | Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
title_fullStr | Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
title_full_unstemmed | Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
title_short | Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
title_sort | investigation of ezh2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084374/ https://www.ncbi.nlm.nih.gov/pubmed/27793210 http://dx.doi.org/10.1186/s40463-016-0168-9 |
work_keys_str_mv | AT idrissherif investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT lindsaycameron investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT kostiukmorris investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT andrewscolin investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT cotedavidwj investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT oconnelldaniela investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT harrisjeffrey investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT seikalyhadi investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer AT bironvincentl investigationofezh2pathwaysfornovelepigenetictreatmentstrategiesinoropharyngealcancer |