The roles of ING5 in gliomas: a good marker for tumorigenesis and a potential target for gene therapy.
The roles of ING5 in gliomas: a good marker for tumorigenesis and a potential target for gene therapy.
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ING5 在神经胶质瘤中的作用：肿瘤发生的良好标志物和基因治疗的潜在靶点
DOI：
10.18632/oncotarget.17802
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发表时间：
2017-08-22
期刊：
影响因子：
--
通讯作者：
Zheng HC
中科院分区：
文献类型：
--
作者：
Zhao S;Zhao ZJ;He HY;Wu JC;Ding XQ;Yang L;Jia N;Li ZJ;Zheng HC
为了阐明ING 5对胶质瘤细胞的抗肿瘤作用及其分子机制，我们在U87细胞中过表达ING 5，并检测其表型及其相关分子。发现ING 5过表达抑制U87细胞的增殖、能量代谢、迁移、侵袭，并诱导G2/M期阻滞、凋亡、去分化、衰老、间充质-上皮转化和对顺铂、MG 132、紫杉醇和SAHA的化学抗性。ING 5转染细胞中N-cadherin、Twist、Slug、Zeb 1、Zeb 2、Snail、Ac-H3、Ac-H4、Cdc 2、Cdk 4和XIAP的表达较低，而Claudin 1、Histones 3和4、p21、p53、Bax、β-catenin、PI 3 K、Akt和p-Akt的表达较高。ING 5过表达可通过抑制细胞增殖和诱导细胞凋亡抑制U87裸鼠移植瘤的生长。ING 5表达下调与胶质瘤的发生和组织发生密切相关。提示ING 5的表达可作为胶质瘤发生和组织发生的良好标志物。它可能成为胶质瘤基因治疗的潜在靶点。PI 3 K/Akt或β-catenin/TCF-4激活可能与化疗耐药性正相关，由ING 5介导。
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants. ING5 overexpression suppressed tumor growth of U87 cells in nude mice by inhibiting proliferation and inducing apoptosis. Down-regulated ING5 expression was closely linked to the tumorigenesis and histogenesis of glioma. These data indicated that ING5 expression might be considered as a good marker for the tumorigenesis and histogenesis of gliomas. It might be employed as a potential target for gene therapy of glioma. PI3K/Akt or β-catenin/TCF-4 activation might be positively linked to chemotherapeutic resistance, mediated by ING5.
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作者：
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作者：
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作者：
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