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CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells

Chromodomain-helicase-DNA-binding protein 4 (CHD4), a core subunit of the nucleosome remodeling and deacetylation (NuRD) complex is highly expressed in several cancers. However, its role in the pathogenesis and progression of papillary thyroid carcinoma (PTC) has not been investigated. We investigat...

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Autores principales: Pratheeshkumar, Poyil, Siraj, Abdul K., Divya, Sasidharan Padmaja, Parvathareddy, Sandeep Kumar, Alobaisi, Khadija, Al-Sobhi, Saif S., Al-Dayel, Fouad, Al-Kuraya, Khawla S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825451/
https://www.ncbi.nlm.nih.gov/pubmed/33419089
http://dx.doi.org/10.3390/ijms22020504
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author Pratheeshkumar, Poyil
Siraj, Abdul K.
Divya, Sasidharan Padmaja
Parvathareddy, Sandeep Kumar
Alobaisi, Khadija
Al-Sobhi, Saif S.
Al-Dayel, Fouad
Al-Kuraya, Khawla S.
author_facet Pratheeshkumar, Poyil
Siraj, Abdul K.
Divya, Sasidharan Padmaja
Parvathareddy, Sandeep Kumar
Alobaisi, Khadija
Al-Sobhi, Saif S.
Al-Dayel, Fouad
Al-Kuraya, Khawla S.
author_sort Pratheeshkumar, Poyil
collection PubMed
description Chromodomain-helicase-DNA-binding protein 4 (CHD4), a core subunit of the nucleosome remodeling and deacetylation (NuRD) complex is highly expressed in several cancers. However, its role in the pathogenesis and progression of papillary thyroid carcinoma (PTC) has not been investigated. We investigated the prognostic significance of CHD4 in a large cohort of Middle Eastern PTC patients and explored the functional role of CHD4 in regulating cancer stemness and EMT in PTC cells. CHD4 overexpression was observed in 45.3% (650/1436) of PTCs, and was associated with aggressive clinico-pathological parameters and worse outcome. Functional analysis using PTC cell lines showed that forced expression of CHD4 promoted cell proliferation, spheroid growth, migration, invasion and progression of epithelial to mesenchymal transition (EMT) in PTC cells whereas its knockdown reversed the effect. Methylation of E-cadherin was associated with loss of expression in CHD4 expressing cells, while CHD4 depletion reactivated E-cadherin expression. Most importantly, knockdown of mesenchymal transcriptional factors, Snail1 or Zeb1, attenuated the spheroid growth in CHD4 expressing PTC cells, showing a potential link between EMT activation and stemness maintenance in PTC. These findings suggest that CHD4 might be a promising therapeutic target in the treatment of patients with an aggressive subtype of PTC.
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spelling pubmed-78254512021-01-24 CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells Pratheeshkumar, Poyil Siraj, Abdul K. Divya, Sasidharan Padmaja Parvathareddy, Sandeep Kumar Alobaisi, Khadija Al-Sobhi, Saif S. Al-Dayel, Fouad Al-Kuraya, Khawla S. Int J Mol Sci Article Chromodomain-helicase-DNA-binding protein 4 (CHD4), a core subunit of the nucleosome remodeling and deacetylation (NuRD) complex is highly expressed in several cancers. However, its role in the pathogenesis and progression of papillary thyroid carcinoma (PTC) has not been investigated. We investigated the prognostic significance of CHD4 in a large cohort of Middle Eastern PTC patients and explored the functional role of CHD4 in regulating cancer stemness and EMT in PTC cells. CHD4 overexpression was observed in 45.3% (650/1436) of PTCs, and was associated with aggressive clinico-pathological parameters and worse outcome. Functional analysis using PTC cell lines showed that forced expression of CHD4 promoted cell proliferation, spheroid growth, migration, invasion and progression of epithelial to mesenchymal transition (EMT) in PTC cells whereas its knockdown reversed the effect. Methylation of E-cadherin was associated with loss of expression in CHD4 expressing cells, while CHD4 depletion reactivated E-cadherin expression. Most importantly, knockdown of mesenchymal transcriptional factors, Snail1 or Zeb1, attenuated the spheroid growth in CHD4 expressing PTC cells, showing a potential link between EMT activation and stemness maintenance in PTC. These findings suggest that CHD4 might be a promising therapeutic target in the treatment of patients with an aggressive subtype of PTC. MDPI 2021-01-06 /pmc/articles/PMC7825451/ /pubmed/33419089 http://dx.doi.org/10.3390/ijms22020504 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pratheeshkumar, Poyil
Siraj, Abdul K.
Divya, Sasidharan Padmaja
Parvathareddy, Sandeep Kumar
Alobaisi, Khadija
Al-Sobhi, Saif S.
Al-Dayel, Fouad
Al-Kuraya, Khawla S.
CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells
title CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells
title_full CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells
title_fullStr CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells
title_full_unstemmed CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells
title_short CHD4 Predicts Aggressiveness in PTC Patients and Promotes Cancer Stemness and EMT in PTC Cells
title_sort chd4 predicts aggressiveness in ptc patients and promotes cancer stemness and emt in ptc cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825451/
https://www.ncbi.nlm.nih.gov/pubmed/33419089
http://dx.doi.org/10.3390/ijms22020504
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