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Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer
Aims: Aberrant hypermethylation of CpG islands is an important hallmark of colorectal cancer (CRC). We previously utilized methyl-DNA immunoprecipitation assays to identify a novel methylated gene, chondrolectin (CHODL), preferentially methylated in human CRC. In this study, we examined the epigenet...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086254/ https://www.ncbi.nlm.nih.gov/pubmed/32226505 http://dx.doi.org/10.7150/jca.38815 |
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author | Zhang, Xinyue Wu, Kaiming Huang, Yuhua Xu, Lixia Li, Xiaoxing Zhang, Ning |
author_facet | Zhang, Xinyue Wu, Kaiming Huang, Yuhua Xu, Lixia Li, Xiaoxing Zhang, Ning |
author_sort | Zhang, Xinyue |
collection | PubMed |
description | Aims: Aberrant hypermethylation of CpG islands is an important hallmark of colorectal cancer (CRC). We previously utilized methyl-DNA immunoprecipitation assays to identify a novel methylated gene, chondrolectin (CHODL), preferentially methylated in human CRC. In this study, we examined the epigenetic inactivation, biological effects and prognostic significance of CHODL in CRC. Main methods: The methylation status of CHODL in CRC was evaluated by bisulfite genomic sequencing (BGS). The functions of CHODL in CRC were determined by proliferation, apoptosis, cell migration and invasion assays. The impact and underlying mechanisms of CHODL in CRC were characterized by western blot and RNA-Seq analyses. The association between CHODL and CRC clinical features was examined using The Cancer Genome Atlas (TCGA) database and immunohistochemical staining. Key findings: CHODL was downregulated in 10 CRC cell lines and CRC tissues, and promoter hypermethylation contributed to its inactivation. Ectopic expression of CHODL inhibited colony formation, suppressed cell viability, induced apoptosis, and restrained cell migration and invasion in vitro and in vivo. Furthermore, high CHODL expression in CRC was a predictor of improved survival, though CHODL hypermethylation was a poor prognostic factor for CRC patients, especially those with early-stage CRC. Significance: CHODL promoter hypermethylation silences CHODL expression in CRC, and CHODL suppresses CRC tumorigenesis. CHODL methylation and expression levels can be used as potential markers to evaluate the prognosis of CRC patients. |
format | Online Article Text |
id | pubmed-7086254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-70862542020-03-27 Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer Zhang, Xinyue Wu, Kaiming Huang, Yuhua Xu, Lixia Li, Xiaoxing Zhang, Ning J Cancer Research Paper Aims: Aberrant hypermethylation of CpG islands is an important hallmark of colorectal cancer (CRC). We previously utilized methyl-DNA immunoprecipitation assays to identify a novel methylated gene, chondrolectin (CHODL), preferentially methylated in human CRC. In this study, we examined the epigenetic inactivation, biological effects and prognostic significance of CHODL in CRC. Main methods: The methylation status of CHODL in CRC was evaluated by bisulfite genomic sequencing (BGS). The functions of CHODL in CRC were determined by proliferation, apoptosis, cell migration and invasion assays. The impact and underlying mechanisms of CHODL in CRC were characterized by western blot and RNA-Seq analyses. The association between CHODL and CRC clinical features was examined using The Cancer Genome Atlas (TCGA) database and immunohistochemical staining. Key findings: CHODL was downregulated in 10 CRC cell lines and CRC tissues, and promoter hypermethylation contributed to its inactivation. Ectopic expression of CHODL inhibited colony formation, suppressed cell viability, induced apoptosis, and restrained cell migration and invasion in vitro and in vivo. Furthermore, high CHODL expression in CRC was a predictor of improved survival, though CHODL hypermethylation was a poor prognostic factor for CRC patients, especially those with early-stage CRC. Significance: CHODL promoter hypermethylation silences CHODL expression in CRC, and CHODL suppresses CRC tumorigenesis. CHODL methylation and expression levels can be used as potential markers to evaluate the prognosis of CRC patients. Ivyspring International Publisher 2020-02-28 /pmc/articles/PMC7086254/ /pubmed/32226505 http://dx.doi.org/10.7150/jca.38815 Text en © The author(s) 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 Zhang, Xinyue Wu, Kaiming Huang, Yuhua Xu, Lixia Li, Xiaoxing Zhang, Ning Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer |
title | Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer |
title_full | Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer |
title_fullStr | Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer |
title_full_unstemmed | Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer |
title_short | Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer |
title_sort | promoter hypermethylation of chodl contributes to carcinogenesis and indicates poor survival in patients with early-stage colorectal cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086254/ https://www.ncbi.nlm.nih.gov/pubmed/32226505 http://dx.doi.org/10.7150/jca.38815 |
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