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Updated: Feb 2, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
CagA increases DNA methylation and decreases PTEN expression in human gastric cancer
Baogui Zhang1, Xiaobei Zhang2, Meng Jin1
1Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China.
Abstract:
Gastric cancer is one of the leading causes of cancer-associated mortality worldwide. Cytotoxin‑associated gene A (CagA) has been reported to be associated with gastric diseases. Phosphatase and tensin homolog (PTEN) and tet methylcytosine dioxygenase 1 (Tet1) are important tumor‑suppressor genes. The present study aimed to investigate the underlying functions of CagA in human gastric cancer, and to explore the associations between CagA, PTEN and Tet1 in gastric cancer. For that purpose, CagA overexpression and Tet1 interference recombinant lentiviral plasmids were constructed. Quantitative polymerase chain reaction (qPCR) was utilized to screen gene expression in HGC‑27 human gastric cancer cells overexpressing CagA. qPCR and western blotting were used to detect gene and protein expression, respectively. In addition, the methylation status of PTEN was detected by methylation‑specific PCR. The expression levels of PTEN, Tet1, apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC)3A, APOBEC3C and APOBEC3F were significantly decreased in the CagA overexpression group compared with in the negative control group in HGC‑27 cells. Compared with in the negative control group, the mRNA and protein expression levels of PTEN were markedly decreased in cells with Tet1 interference. The decreased expression of PTEN was associated with increased methylation levels in the cells. In addition, the protein expression levels of PTEN were significantly decreased in HGC‑27 cells when CagA was overexpressed. The expression levels of PTEN and Tet1 were also markedly decreased in CagA+ gastric cancer tissues compared with in non‑cancerous tissues. The decreased expression of PTEN in CagA+ gastric cancer tissues was associated with increased methylation levels. In conclusion, overexpression of CagA significantly decreased the expression of PTEN, Tet1, APOBEC3A, APOBEC3C and APOBEC3F in human gastric cancer. In addition, CagA increased DNA methylation and decreased PTEN expression, which was reversed by Tet1 overexpression. The present study may facilitate future therapeutic approaches targeting human gastric cancer.
Insights
Cytotoxin-associated gene A (CagA) in gastric cancer reduces tumor suppressor genes PTEN and Tet1. CagA also increases DNA methylation, leading to decreased PTEN, but Tet1 overexpression can reverse this effect.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Gastric cancer is a leading cause of cancer mortality globally.
- Cytotoxin-associated gene A (CagA) is linked to gastric diseases.
- PTEN and Tet1 are crucial tumor suppressor genes.
Purpose of the Study:
- Investigate CagA's function in human gastric cancer.
- Explore the relationship between CagA, PTEN, and Tet1 in gastric cancer.
Main Methods:
- Constructed CagA overexpression and Tet1 interference lentiviral plasmids.
- Utilized qPCR and Western blotting for gene and protein expression analysis.
- Assessed PTEN methylation status using methylation-specific PCR.
Main Results:
- CagA overexpression decreased PTEN, Tet1, and APOBEC3 gene/protein expression in HGC-27 cells.
- Tet1 interference reduced PTEN expression, associated with increased DNA methylation.
- CagA+ gastric cancer tissues showed decreased PTEN and Tet1 expression compared to non-cancerous tissues.
Conclusions:
- CagA overexpression significantly downregulates PTEN, Tet1, and APOBEC3 family members in gastric cancer.
- CagA promotes DNA methylation and reduces PTEN expression, an effect reversible by Tet1.
- Findings may inform future therapeutic strategies for gastric cancer.
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