DNMT1 通过 TGF-β 介导的 MST1 抑制促进神经胶质瘤恶性转化。

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

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230601, China.

Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei 230601, China; Department of Neurosurgery, Cancer Hospital, National Cancer Centre of China, Chinese Academy of Medical Sciences, Peking Union Medical College, 17 Panjiayuan Nanli, Beijing 100021, China.

出版信息

Biomed Pharmacother. 2017 Oct;94:774-780. doi: 10.1016/j.biopha.2017.07.081. Epub 2017 Aug 9.

DOI:10.1016/j.biopha.2017.07.081

PMID:28802229

Abstract

Human gliomas are related to high rates of morbidity and mortality. TGF-β 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-β are not fully elucidated. Here, we showed that TGF-β 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-β-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-β-induced proliferation, migration and invasiveness in glioma cells. These results suggest that TGF-β promotes glioma malignancy through DNMT1-mediated loss of MST1 expression.

摘要

人胶质瘤与高发病率和死亡率有关。TGF-β促进神经胶质瘤细胞的生长，并与人类神经胶质瘤的恶性程度相关。然而，TGF-β 发挥恶性功能的分子机制尚未完全阐明。在这里，我们表明 TGF-β 诱导 U87 和 U251 神经胶质瘤细胞中 MST1 表达下调。用 DNA 甲基化抑制剂 5-氮杂-2'-脱氧胞苷（5-AzadC）处理神经胶质瘤细胞可防止 MST1 表达的丢失。添加 5-AzadC 还降低了 TGF-β 刺激的神经胶质瘤细胞增殖、迁移和侵袭。此外，DNMT1 的敲低在上皮样神经胶质瘤细胞中上调了 MST1 的表达。此外，DNMT1 的抑制阻断了 TGF-β 诱导的神经胶质瘤细胞的增殖、迁移和侵袭。这些结果表明，TGF-β 通过 DNMT1 介导的 MST1 表达缺失促进神经胶质瘤的恶性转化。