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Updated: May 4, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis
Thaís Brilhante Pontes1, Elizabeth Suchi Chen, Carolina Oliveira Gigek
1Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740 - Ed. Leitão da Cunha - 1ºandar, São Paulo, 04023-900, SP, Brazil.
Abstract:
Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia.
Insights
Reduced expression of methyl-CpG-binding domain (MBD) proteins MBD2 and MBD3 is linked to gastric cancer development. DNA methylation appears to play a minor role in regulating these genes in gastric carcinogenesis.
Area of Science:
- Molecular Oncology
- Epigenetics
- Gastric Carcinogenesis
Background:
- Aberrant DNA methylation is a hallmark of various cancers, including gastric cancer.
- Methyl-CpG-binding domain (MBD) proteins are crucial for chromatin remodeling and gene expression regulation.
- The specific roles of MBD2 and MBD3 in gastric carcinogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the messenger RNA (mRNA) levels and promoter methylation patterns of MBD2 and MBD3 in gastric tissues.
- To evaluate the association between MBD2 and MBD3 expression and clinicopathological characteristics in gastric cancer.
- To elucidate the potential role of DNA methylation in regulating MBD2 and MBD3 expression during gastric carcinogenesis.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to determine MBD2 and MBD3 mRNA levels.
- Bisulfite sequencing was employed to analyze the promoter methylation status of MBD2 and MBD3.
- Samples included neoplastic gastric tissues, adjacent nonneoplastic tissues, gastritis, and non-gastritis tissues.
Main Results:
- Significantly reduced MBD2 and MBD3 mRNA levels were observed in neoplastic gastric tissues compared to other groups.
- Neoplastic tissues displayed higher MBD2 promoter methylation, while MBD3 promoter methylation was notable in the non-gastritis group.
- A strong correlation was found between MBD2 and MBD3 expression levels, but a weak correlation between gene expression and promoter methylation.
Conclusions:
- Reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis.
- DNA methylation appears to play a limited role in the direct regulation of MBD2 and MBD3 expression in this context.
- Further research is warranted to fully understand the epigenetic mechanisms, including methylation at specific CpG sites, involved in gastric neoplasia.
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