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CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer
Colorectal cancer (CRC) has ranked first in terms of incidence in Taiwan. Surgical resection combined with chemo-, radio-, or targeted-therapies are the main treatments for CRC patients in current clinical practice. However, many CRC patients still respond poorly to these treatments, leading to tumo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120460/ https://www.ncbi.nlm.nih.gov/pubmed/33994851 http://dx.doi.org/10.7150/ijbs.56976 |
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author | Chang, Chia-Lo Huang, Chi-Ruei Chang, Shu-Jyuan Wu, Chun-Chieh Chen, Hong-Hwa Luo, Chi-Wen Yip, Hon-Kan |
author_facet | Chang, Chia-Lo Huang, Chi-Ruei Chang, Shu-Jyuan Wu, Chun-Chieh Chen, Hong-Hwa Luo, Chi-Wen Yip, Hon-Kan |
author_sort | Chang, Chia-Lo |
collection | PubMed |
description | Colorectal cancer (CRC) has ranked first in terms of incidence in Taiwan. Surgical resection combined with chemo-, radio-, or targeted-therapies are the main treatments for CRC patients in current clinical practice. However, many CRC patients still respond poorly to these treatments, leading to tumor recurrence and an unacceptably high incidence of metastasis and death. Therefore, appropriate diagnosis, treatment, and drug selection are pressing issues in clinical practice. The Mi-2/nucleosome remodeling and deacetylase complex is an important epigenetic regulator of chromatin structure and gene expression. An important component of this complex is chromodomain-helicase-DNA-binding protein 4 (CHD4), which is involved in DNA repair after injury. Recent studies have indicated that CHD4 has oncogenic functions that inhibit multiple tumor suppressor genes through epigenetic regulation. However, the role of CHD4 in CRC has not yet been well investigated. In this study, we compared CHD4 expression in CRC patients from The Cancer Genome Atlas database. We found higher levels of CHD4 expression in CRC patients. In a series of in vitro experiments, we found that CHD4 affected cell motility and drug sensitivity in CRC cells. In animal models, the depletion of CHD4 affected CRC tumor growth, and the combination of a histone deacetylase 1 (HDAC1) inhibitor and platinum drugs inhibited CHD4 expression and increased the cytotoxicity of platinum drugs. Moreover, CHD4 expression was also a prognostic biomarker in CRC patients. Based on the above results, we believe that CHD4 expression is a viable biomarker for predicting metastasis CRC patients, and it has the potential to become a target for drug development. |
format | Online Article Text |
id | pubmed-8120460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-81204602021-05-14 CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer Chang, Chia-Lo Huang, Chi-Ruei Chang, Shu-Jyuan Wu, Chun-Chieh Chen, Hong-Hwa Luo, Chi-Wen Yip, Hon-Kan Int J Biol Sci Research Paper Colorectal cancer (CRC) has ranked first in terms of incidence in Taiwan. Surgical resection combined with chemo-, radio-, or targeted-therapies are the main treatments for CRC patients in current clinical practice. However, many CRC patients still respond poorly to these treatments, leading to tumor recurrence and an unacceptably high incidence of metastasis and death. Therefore, appropriate diagnosis, treatment, and drug selection are pressing issues in clinical practice. The Mi-2/nucleosome remodeling and deacetylase complex is an important epigenetic regulator of chromatin structure and gene expression. An important component of this complex is chromodomain-helicase-DNA-binding protein 4 (CHD4), which is involved in DNA repair after injury. Recent studies have indicated that CHD4 has oncogenic functions that inhibit multiple tumor suppressor genes through epigenetic regulation. However, the role of CHD4 in CRC has not yet been well investigated. In this study, we compared CHD4 expression in CRC patients from The Cancer Genome Atlas database. We found higher levels of CHD4 expression in CRC patients. In a series of in vitro experiments, we found that CHD4 affected cell motility and drug sensitivity in CRC cells. In animal models, the depletion of CHD4 affected CRC tumor growth, and the combination of a histone deacetylase 1 (HDAC1) inhibitor and platinum drugs inhibited CHD4 expression and increased the cytotoxicity of platinum drugs. Moreover, CHD4 expression was also a prognostic biomarker in CRC patients. Based on the above results, we believe that CHD4 expression is a viable biomarker for predicting metastasis CRC patients, and it has the potential to become a target for drug development. Ivyspring International Publisher 2021-04-12 /pmc/articles/PMC8120460/ /pubmed/33994851 http://dx.doi.org/10.7150/ijbs.56976 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Chang, Chia-Lo Huang, Chi-Ruei Chang, Shu-Jyuan Wu, Chun-Chieh Chen, Hong-Hwa Luo, Chi-Wen Yip, Hon-Kan CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
title | CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
title_full | CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
title_fullStr | CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
title_full_unstemmed | CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
title_short | CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
title_sort | chd4 as an important mediator in regulating the malignant behaviors of colorectal cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120460/ https://www.ncbi.nlm.nih.gov/pubmed/33994851 http://dx.doi.org/10.7150/ijbs.56976 |
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