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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7825451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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