TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy

被引：29

作者：

Guo, Zhifei ^{[1
]}

Li, Guangyuan ^{[1
]}

Bian, Erbao ^{[1
]}

Ma, Chun-Chun ^{[1
]}

Wan, Jinghai ^{[1
,2
]}

Zhao, Bing ^{[1
]}

机构：

[1] Anhui Med Univ, Affiliated Hosp 2, Dept Neurosurg, Hefei 230601, Anhui, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Natl Canc Ctr China, Dept Neurosurg, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2017年 / 94卷

关键词：

Glioma; MST1; DNMT1; DNA METHYLATION; PROTEIN EXPRESSION; HYPERMETHYLATION; GROWTH; GENE; EZH2;

D O I：

10.1016/j.biopha.2017.07.081

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Human gliomas are related to high rates of morbidity and mortality. TGF-beta promotes the growth of glioma cells, and correlate with the degree of malignancy of human gliomas. However, the molecular mechanisms involved in the malignant function of TGF-beta are not fully elucidated. Here, we showed that TGF-beta induced the downregulation of MST1 expression in U87 and U251 glioma cells. Treatment of glioma cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC) prevented the loss of MST1 expression. Addition of 5-AzadC also reduced the TGF-beta-stimulated proliferation, migration and invasiveness of glioma cells. Furthermore, Knockdown of DNMT1 upregulated MST1 expression in gliomas cells. In addition, the inhibition of DNMT1 blocked TGF-beta-induced proliferation, migration and invasiveness in glioma cells. These results suggest that TGF-beta promotes glioma malignancy through DNMT1-mediated loss of MST1 expression. (C) 2017 Published by Elsevier Masson SAS.

引用

页码：774 / 780

页数：7

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