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

Autor: Beibei Yang, Ying Zhang, Pinli Yue, Yuchen Jiao, Mo Li, Pei Wang, Mingzhou Guo, Yifei Li, Jinge Song, Dandan Zhang, Huihui Yin, Qing Zhu, Aiai Gao, Yun Liu, Yarui Ma, Siyuan He, Xiaobing Wang
Rok vydání: 2019
Předmět:
0301 basic medicine
Methylation changes
Epithelial dysplasia
Esophageal Neoplasms
Carcinogenesis
Bisulfite sequencing
Whole genome bisulfite sequencing
Down-Regulation
Biology
medicine.disease_cause
Decitabine
Malignant transformation
Epigenesis
Genetic
03 medical and health sciences
Mice
0302 clinical medicine
Esophageal squamous cell carcinoma
Exome Sequencing
Genetics
medicine
Gene silencing
Animals
Humans
Epigenetics
Gene Silencing
Enzyme Inhibitors
Promoter Regions
Genetic
Molecular Biology
Genetics (clinical)
Mice
Inbred BALB C
Research
Receptor
Transforming Growth Factor-beta Type II
Cancer diagnosis
Methylation
Cell cycle
DNA Methylation
TGFBR2
G2 Phase Cell Cycle Checkpoints
Treatment
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Heterografts
Female
Developmental Biology
Zdroj: Clinical Epigenetics
ISSN: 1868-7083
Popis: 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.
Databáze: OpenAIRE
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