S100A4 hypomethylation affects epithelial–mesenchymal transition partially induced by LMP2A in nasopharyngeal carcinoma
Zhe Lin
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorLei Deng
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorJie Ji
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorCi Cheng
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorXin Wan
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorRunqiu Jiang
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorJunwei Tang
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorHan Zhuo
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorCorresponding Author
Beicheng Sun
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Correspondence to: Department of Immunology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province, P.R. China.
Correspondence: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, P.R. China.
Search for more papers by this authorYun Chen
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorZhe Lin
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorLei Deng
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorJie Ji
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorCi Cheng
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorXin Wan
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorRunqiu Jiang
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorJunwei Tang
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorHan Zhuo
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorCorresponding Author
Beicheng Sun
Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Correspondence to: Department of Immunology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province, P.R. China.
Correspondence: Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, P.R. China.
Search for more papers by this authorYun Chen
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu Province, China
Search for more papers by this authorAbstract
To identify cellular target genes involved in NPC cell invasion and metastasis, gene expression profiles of CNE-1 cells with or without ectopic LMP2A expression were compared by using the metastatic gene array. S100 calcium binding protein A4 (S100A4) was the highest increased one among these genes both in mRNA and protein levels of NPC cells. Moreover, S100A4 was upregulated in LMP2A-positive NPC tissues. We found that CNE-1-S100A4 showed significantly increased invasion ability as compared to the controls both in vitro and in vivo, which indicated that S100A4 induced EMT occurrence and promoted metastasis. Notably, the DNA hypomethylation of S100A4 was found in LMP2A-positive NPC tissues. Besides, inhibition of DNA methyltransferases via 5-Aza-dC stimulated the expression of S100A4 in the cells without ectopic LMP2A expression. The methylation changes were confirmed by methylation specific PCR (MSP), suggesting that LMP2A ectopic expression led to the demethylation of S100A4 promoter. These results demonstrated that LMP2A-induced hypomethylation participated in regulating S100A4 expression in NPC. Our findings provide an evidence for the emerging notion that hypomethylation and activation of correlated genes are crucial for metastasis progression in cancer. © 2015 Wiley Periodicals, Inc.
Supporting Information
Additional supporting information may be found in the online version of this article at the publisher's web-site.
| Filename | Description |
|---|---|
| mc22389-sup-0001-SupTab-S1.docx21.1 KB | Table S1. Sequences of primers for real-time PCR and methylation analysis. |
| mc22389-sup-0002-SupFig-S1.tif253.3 KB | Supporting Information Figure. |
| mc22389-sup-0003-SupData-S1.pdf134.6 KB | CNE-1-LMP2A. |
| mc22389-sup-0004-SupData-S2.pdf134.5 KB | CNE-1-Vector. |
| mc22389-sup-0005-SupData-S3.pdf33.5 KB | Human Tumor Metastasis Plate. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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