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.