Methylation Silencing of TGF-β Receptor Type II is Involved in Malignant Transformation of Esophageal Squamous Cell Carcinoma

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2020 Feb 13

PMID 32046777

Citations 14

Authors

Yarui Ma

Siyuan He

Aiai Gao

Ying Zhang

Qing Zhu

Pei Wang

Beibei Yang

Huihui Yin

Yifei Li

Jinge Song

Pinli Yue

Mo Li

Dandan Zhang

Yun Liu

Xiaobing Wang

Mingzhou Guo

Yuchen Jiao

Affiliations

Soon will be listed here.

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.

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