TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy
TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy
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DOI：
10.1016/j.biopha.2017.07.081
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发表时间：
2017-10-01
影响因子：
7.5
通讯作者：
Zhao, Bing
中科院分区：
文献类型：
--
作者：
Guo, Zhifei;Li, Guangyuan;Zhao, Bing
人类神经胶质瘤与高发病率和死亡率有关。tgf - β促进胶质瘤细胞的生长，并与胶质瘤的恶性程度相关。然而，参与tgf - β恶性功能的分子机制尚未完全阐明。在这里，我们发现tgf - β诱导了U87和U251胶质瘤细胞中MST1表达的下调。用DNA甲基化抑制剂5-aza-2'-脱氧胞苷（5-AzadC）治疗胶质瘤细胞可阻止MST1表达的丧失。5-AzadC的加入也降低了tgf - β刺激的胶质瘤细胞的增殖、迁移和侵袭性。此外，DNMT1的下调上调了胶质瘤细胞中MST1的表达。此外，DNMT1的抑制可阻断tgf - β诱导的胶质瘤细胞的增殖、迁移和侵袭。这些结果表明tgf - β通过dnmt1介导的MST1表达缺失促进胶质瘤恶性肿瘤的发生。(C) 2017年由Elsevier Masson SAS出版。
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.