Hypoxia-induced miR-497 decreases glioma cell sensitivity to TMZ by inhibiting apoptosis

被引:49
|
作者
Lan, Jin [1 ]
Xue, Yajun [1 ]
Chen, Huairui [1 ]
Zhao, Sanhu [1 ]
Wu, Zhijian [1 ]
Fang, Jun [1 ]
Han, Cong [1 ]
Lou, Meiqing [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Affiliated Peoples Hosp 1, Shanghai 200030, Peoples R China
关键词
miR-497; PDCD4; Drug resistance; Glioma; MICRORNA;
D O I
10.1016/j.febslet.2014.07.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Understanding the resistance of glioma cells to chemotherapy has been an enormous challenge. In particular, mechanisms by which tumor cells acquire resistance to chemotherapy under hypoxic conditions are not fully understood. In this study, we have found that miR-497 is overexpressed in glioma and that hypoxia can induce the expression of miR-497 at the transcriptional level by binding with the hypoxia response element in the promoter. Ectopic overexpression of miR-497 promotes chemotherapy resistance in glioma cells by targeting PDCD4, a tumor suppressor that is involved in apoptosis. In contrast, the inhibition of miR-497 enhances apoptosis and increases the sensitivity of glioma cells to TMZ. These results suggest that miR-497 is a potential molecular target for glioma therapy. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3333 / 3339
页数:7
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