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

被引：17

作者：

Ma, Yarui ^{[1
,2
]}

He, Siyuan ^{[1
,2
]}

Gao, Aiai ^{[3
]}

Zhang, Ying ^{[1
,2
]}

Zhu, Qing ^{[1
,2
]}

Wang, Pei ^{[1
,2
]}

Yang, Beibei ^{[1
,2
]}

Yin, Huihui ^{[1
,2
]}

Li, Yifei ^{[1
,2
]}

Song, Jinge ^{[1
,2
]}

Yue, Pinli ^{[1
,2
]}

Li, Mo ^{[1
,2
]}

Zhang, Dandan ^{[4
,5
]}

Liu, Yun ^{[4
,5
]}

Wang, Xiaobing ^{[1
,2
]}

Guo, Mingzhou ^{[3
]}

Jiao, Yuchen ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Canc Hosp, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Natl Canc Ctr, Beijing 100021, Peoples R China

[2] Peking Union Med Coll, Res Bldg,17 Panjiayuan Nanli, Beijing 100021, Peoples R China

[3] Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Res Bldg,28 Fuxing Rd, Beijing 100853, Peoples R China

[4] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, MOE Key Lab Metab & Mol Med, Shanghai 200032, Peoples R China

[5] Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China

来源：

CLINICAL EPIGENETICS | 2020年 / 12卷 / 01期

关键词：

Esophageal squamous cell carcinoma; Whole genome bisulfite sequencing; TGFBR2; Methylation changes; Cancer diagnosis; Treatment; DNA METHYLATION; PROMOTER METHYLATION; BLADDER-CANCER; HYPERMETHYLATION; GENE; EXPRESSION; EPIDEMIOLOGY; INSTABILITY; PROGRESSION; MECHANISMS;

D O I：

10.1186/s13148-020-0819-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-beta receptor type II (TGFBR2), an important mediator of TGF-beta 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.

引用

页数：12