Role of gene promoter methylation regulated by TETs and DNMTs in the overexpression of HLA‑G in MCF‑7 cells

Zhang,Daoyu; An,Xinglan; Li,Ziyi; Zhang,Sheng

doi:10.3892/etm.2019.7481

Role of gene promoter methylation regulated by TETs and DNMTs in the overexpression of HLA‑G in MCF‑7 cells

Authors:
- Daoyu Zhang
- Xinglan An
- Ziyi Li
- Sheng Zhang
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Affiliations: State and Local Joint Engineering Laboratory for Animal Models of Human Diseases, Academy of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130061, P.R. China
Published online on: April 11, 2019 https://doi.org/10.3892/etm.2019.7481
Pages: 4709-4714

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Abstract

Human leukocyte antigen‑G (HLA‑G) is highly expressed in numerous solid tumor cell types and has important roles in protecting tumor cells from host immune recognition and destruction. DNA methylation modification, which may regulate gene expression, is aberrant in numerous tumor cell types. However, whether the high expression of HLA‑G in tumor cells is induced by aberrant DNA methylation has remained elusive. In the present study, HLA‑G, DNA methyltransferase (DNMT) and ten‑eleven translocation (TET) expression, as well as the DNA methylation level of HLA‑G, were assessed in the HBL‑100 breast cell line and the MCF‑7 breast cancer cell line. The influence of TET on the expression and DNA methylation levels of HLA‑G in MCF‑7 was assessed through treatment with the TET inhibitor dimethyloxallyl glycine (DMOG). The results indicated that HLA‑G expression was significantly greater in MCF‑7 than that in HBL‑100 cells; however, the DNA methylation level of HLA‑G was lower in MCF‑7 than that in HBL‑100 cells. Furthermore, in MCF‑7 cells, DNMT1 and DNMT3a were expressed at lower levels and TET2 was expressed at higher levels than in HBL‑100 cells. Treatment with DMOG significantly decreased HLA‑G expression, while increasing the DNA methylation level of HLA‑G in MCF‑7. In conclusion, the results indicated that overexpression of HLA‑G in MCF‑7 cells was induced by DNA methylation modification. The lower DNMT1 and DNMT3a and higher TET2 expression levels may be responsible for the abnormal DNA methylation of HLA‑G in MCF‑7. Treatment with TET inhibitor prevented aberrant HLA‑G expression and DNA methylation in MCF‑7. The present study may provide potential targets for novel anti‑cancer drugs.

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