Overexpression of DCF1 inhibits glioma through destruction of mitochondria and activation of apoptosis pathway.
Overexpression of DCF1 inhibits glioma through destruction of mitochondria and activation of apoptosis pathway.
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DCF1的过表达通过破坏线粒体和激活细胞凋亡途径抑制神经胶质瘤
DOI：
10.1038/srep03702
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发表时间：
2014-01-15
影响因子：
4.6
通讯作者：
Wen T
中科院分区：
文献类型：
--
作者：
Xie Y;Li Q;Yang Q;Yang M;Zhang Z;Zhu L;Yan H;Feng R;Zhang S;Huang C;Liu Z;Wen T
神经胶质瘤是影响中枢神经系统的最常见的脑肿瘤，并且与高死亡率相关。DCF 1是一种膜蛋白，以前发现在神经干细胞分化中发挥作用。在本研究中，我们发现dcf 1的过表达显着抑制细胞增殖，迁移和侵袭，并显着促进胶质母细胞瘤U251细胞系的凋亡。DCF 1功能区的缺失突变表明，DCF 1的完整结构是细胞凋亡所必需的。此外，在无胸腺裸鼠中观察到显著较低的致瘤性，通过移植过表达dcf 1的U251细胞。为探讨dcf 1诱导胶质瘤细胞凋亡的机制，我们对胶质瘤细胞线粒体结构和膜电位进行了研究，结果发现dcf 1诱导胶质瘤细胞线粒体肿胀，嵴破坏，膜电位明显下降。机制上，caspase-3信号被激活。最后，研究了U251细胞中的内源性dcf 1沉默。结果显示，dcf 1基因启动子序列的-1339和-1322位高度甲基化，揭示了dcf 1基因与致瘤性之间的因果关系。本研究发现了一种以前未知的涉及dcf 1过表达的肿瘤细胞凋亡机制，并为治疗胶质瘤患者提供了一种新的方法。
Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To decode the apoptosis induced by dcf1, mitochondrial structure and membrane potential in glioma cells were investigated and the results indicated obvious mitochondrial swelling, destruction of cristae, and a significant decline in membrane potential. Mechanismly, caspase-3 signaling was activated. Finally, endogenous dcf1 silence in U251 cells was investigated. Results showed a highly methylation at −1339 and −1322 position at dcf1 promoter sequence, revealing the causal relationship between dcf1 gene and tumorigencicity. The present study identified a previously unknown cancer apoptosis mechanism involving dcf1 overexpression and provided a novel approach to potentially treat glioma patients.
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胶质瘤干细胞增殖和肿瘤生长由一氧化氮合酶2促进。
影响因子：
64.5
作者：
Eyler CE;Wu Q;Yan K;MacSwords JM;Chandler-Militello D;Misuraca KL;Lathia JD;Forrester MT;Lee J;Stamler JS;Goldman SA;Bredel M;McLendon RE;Sloan AE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
影响因子：
64.5
作者：
Chipuk JE;McStay GP;Bharti A;Kuwana T;Clarke CJ;Siskind LJ;Obeid LM;Green DR
通讯作者：
Green DR
MicroRNA-351 调节 TMEM59 (DCF1) 表达并介导神经干细胞形态发生
影响因子：
4.1
作者：
Li, Xiao;Feng, Ruili;Wen, Tieqiao
通讯作者：
Wen, Tieqiao
影响因子：
64.5
作者：
Li Z;Jo J;Jia JM;Lo SC;Whitcomb DJ;Jiao S;Cho K;Sheng M
通讯作者：
Sheng M
影响因子：
11.4
作者：
Benard, Giovanni;Neutzner, Albert;Karbowski, Mariusz
通讯作者：
Karbowski, Mariusz