2. Academic Validation
  3. Methylation silencing of TGF-β receptor type II is involved in malignant transformation of esophageal squamous cell carcinoma

Methylation silencing of TGF-β receptor type II is involved in malignant transformation of esophageal squamous cell carcinoma

  • Clin Epigenetics. 2020 Feb 11;12(1):25. doi: 10.1186/s13148-020-0819-6.
Yarui Ma 1,  Siyuan He 1,  Aiai Gao 2,  Ying Zhang 1,  Qing Zhu 1,  Pei Wang 1,  Beibei Yang 1,  Huihui Yin 1,  Yifei Li 1,  Jinge Song 1,  Pinli Yue 1,  Mo Li 1,  Dandan Zhang 3,  Yun Liu 3,  Xiaobing Wang 4,  Mingzhou Guo 5,  Yuchen Jiao 6
Affiliations

Affiliations

  • 1 State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Research Building, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
  • 2 Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Research Building, No.28 Fuxing Road, Haidian District, Beijing, 100853, China.
  • 3 MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 4 State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Research Building, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. wangxb@cicams.ac.cn.
  • 5 Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Research Building, No.28 Fuxing Road, Haidian District, Beijing, 100853, China. mzguo@hotmail.com.
  • 6 State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Research Building, No.17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China. Jiaoyuchen@cicams.ac.cn.
PMID: 32046777 DOI: 10.1186/s13148-020-0819-6
Abstract

Background: Although massive studies have been conducted to investigate the mechanisms of esophageal squamous cell carcinoma (ESCC) carcinogenesis, the understanding of molecular alterations during the malignant transformation of epithelial dysplasia is still lacking, especially regarding epigenetic changes.

Results: To better characterize the methylation changes during the malignant transformation of epithelial dysplasia, a whole-genome bisulfite Sequencing analysis was performed on a series of tumor, dysplastic, and non-neoplastic epithelial tissue samples from esophageal squamous cell carcinoma (ESCC) patients. Promoter hypermethylation in TGF-β Receptor type II (TGFBR2), an important mediator of TGF-β signaling, was identified. Further, we evaluated the methylation and expression of TGFBR2 in tumor samples through The Cancer Genome Atlas multiplatform data as well as immunohistochemistry. Moreover, treatment of ESCC cell lines with5-Aza-2'-deoxycytidine, a DNA Methyltransferase Inhibitor, reactivated the expression of TGFBR2. The lentiviral mediating the overexpression of TGFBR2 inhibited the proliferation of ESCC cell line by inducing cell cycle G2/M arrest. Furthermore, the overexpression of TGFBR2 inhibited the tumor growth obviously in vivo.

Conclusions: The characterization of methylation silencing of TGFBR2 in ESCC will enable us to further explore whether this epigenetic change could be considered as a predictor of malignant transformation in esophageal epithelial dysplasia and whether use of a TGFBR2 agonist may lead to a new therapeutic strategy in patients with ESCC.

Keywords

Cancer diagnosis; Esophageal squamous cell carcinoma; Methylation changes; TGFBR2; Treatment; Whole genome bisulfite sequencing.

Figures
Products