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Updated: Jun 19, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
CHD5 is down-regulated through promoter hypermethylation in gastric cancer
Xian Wang1, Kenneth K K Lau, Leo K Y So
1Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China. wangx118@yahoo.com
Background:
Nonhistone chromosomal proteins in concert with histones play important roles in the replication and repair of DNA and in the regulation of gene expression. The deregulation of these proteins can contribute to the development of a variety of diseases such as cancer. As a nonhistone chromosomal protein, chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as the product of a novel tumor suppressor gene (TSG), promoting the transcription of p19ink4a and p16arf. The inactivation of CHD5 was achieved partly through genetic deletion since it is located in 1p36, a region frequently deleted in human tumors. In this study, we aim to study the involvement of CHD5 in gastric cancer, the second most common cancer worldwide.
Methods:
CHD5 expression in a panel of gastric cancer cells were determined by quantitative RT-PCR. The methylation of CHD5 was evaluated by methylation specific PCR and bisulfite genome sequencing. The effect of CHD5 on growth of gastric cancer cells was tested by colony formation assay.
Results:
CHD5 expression was down-regulated in all of gastric cancer cell lines used (100%, 7/7) and significantly restored after pharmacological demethylation. Methylation of CHD5 promoter was detected in all of seven gastric cancer cell lines and in the majority of primary gastric carcinoma tissues examined (73%, 11/15). Finally, ectopic expression of CHD5 in gastric cancer cells led to a significant growth inhibition.
Conclusion:
CHD5 was a TSG epigenetically down-regulated in gastric cancer.
Insights
Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor gene in gastric cancer. Its expression is epigenetically silenced by promoter methylation, leading to uncontrolled cell growth.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Nonhistone chromosomal proteins, including chromodomain helicase DNA binding protein 5 (CHD5), are crucial for DNA replication, repair, and gene expression regulation.
- Deregulation of these proteins is linked to various diseases, notably cancer.
- CHD5, a novel tumor suppressor gene (TSG), promotes transcription of p19ink4a and p16arf and is frequently deleted in tumors due to its location at 1p36.
Purpose of the Study:
- To investigate the role of CHD5 in gastric cancer, the second most prevalent cancer globally.
- To determine if CHD5 functions as a tumor suppressor in gastric cancer and the mechanisms underlying its potential inactivation.
Main Methods:
- Quantitative RT-PCR was used to assess CHD5 expression in gastric cancer cell lines.
- Methylation-specific PCR and bisulfite genome sequencing were employed to evaluate CHD5 promoter methylation.
- Colony formation assays were conducted to test the impact of CHD5 on gastric cancer cell growth.
Main Results:
- CHD5 expression was significantly down-regulated in all tested gastric cancer cell lines (100%, 7/7).
- Promoter methylation of CHD5 was detected in all seven gastric cancer cell lines and in 73% (11/15) of primary gastric carcinoma tissues.
- Pharmacological demethylation restored CHD5 expression, and ectopic CHD5 expression inhibited gastric cancer cell growth.
Conclusions:
- CHD5 functions as a tumor suppressor gene in gastric cancer.
- Epigenetic silencing via promoter methylation is a key mechanism for CHD5 down-regulation in gastric cancer.
- Restoring CHD5 expression can inhibit gastric cancer cell proliferation.
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