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Article Open Access

CagA increases DNA methylation and decreases PTEN expression in human gastric cancer

  • Authors:
    • Baogui Zhang
    • Xiaobei Zhang
    • Meng Jin
    • Lei Hu
    • Mingde Zang
    • Weilong Qiu
    • Shouqi Wang
    • Bingya Liu
    • Shiqi Liu
    • Dongli Guo
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China, Department of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China, Department of General Surgery Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China, Department of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 309-319
    |
    Published online on: November 13, 2018
       https://doi.org/10.3892/mmr.2018.9654
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang B, Zhang X, Jin M, Hu L, Zang M, Qiu W, Wang S, Liu B, Liu S, Guo D, Guo D, et al: CagA increases DNA methylation and decreases PTEN expression in human gastric cancer. Mol Med Rep 19: 309-319, 2019.
APA
Zhang, B., Zhang, X., Jin, M., Hu, L., Zang, M., Qiu, W. ... Guo, D. (2019). CagA increases DNA methylation and decreases PTEN expression in human gastric cancer. Molecular Medicine Reports, 19, 309-319. https://doi.org/10.3892/mmr.2018.9654
MLA
Zhang, B., Zhang, X., Jin, M., Hu, L., Zang, M., Qiu, W., Wang, S., Liu, B., Liu, S., Guo, D."CagA increases DNA methylation and decreases PTEN expression in human gastric cancer". Molecular Medicine Reports 19.1 (2019): 309-319.
Chicago
Zhang, B., Zhang, X., Jin, M., Hu, L., Zang, M., Qiu, W., Wang, S., Liu, B., Liu, S., Guo, D."CagA increases DNA methylation and decreases PTEN expression in human gastric cancer". Molecular Medicine Reports 19, no. 1 (2019): 309-319. https://doi.org/10.3892/mmr.2018.9654
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang B, Zhang X, Jin M, Hu L, Zang M, Qiu W, Wang S, Liu B, Liu S, Guo D, Guo D, et al: CagA increases DNA methylation and decreases PTEN expression in human gastric cancer. Mol Med Rep 19: 309-319, 2019.
APA
Zhang, B., Zhang, X., Jin, M., Hu, L., Zang, M., Qiu, W. ... Guo, D. (2019). CagA increases DNA methylation and decreases PTEN expression in human gastric cancer. Molecular Medicine Reports, 19, 309-319. https://doi.org/10.3892/mmr.2018.9654
MLA
Zhang, B., Zhang, X., Jin, M., Hu, L., Zang, M., Qiu, W., Wang, S., Liu, B., Liu, S., Guo, D."CagA increases DNA methylation and decreases PTEN expression in human gastric cancer". Molecular Medicine Reports 19.1 (2019): 309-319.
Chicago
Zhang, B., Zhang, X., Jin, M., Hu, L., Zang, M., Qiu, W., Wang, S., Liu, B., Liu, S., Guo, D."CagA increases DNA methylation and decreases PTEN expression in human gastric cancer". Molecular Medicine Reports 19, no. 1 (2019): 309-319. https://doi.org/10.3892/mmr.2018.9654
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