MicroRNA-153/Nrf-2/GPx1 pathway regulates radiosensitivity and stemness of glioma stem cells via reactive oxygen species

被引：72
作者：
Yang, Wei [1 ]
Shen, Yueming [1 ]
Wei, Jing [1 ]
Liu, Fenju [1 ]
机构：
[1] Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher, Sch Radiol Med & Protect, Dept Radiobiol,Med Coll, Suzhou 215123, Jiangsu, Peoples R China
来源：
ONCOTARGET | 2015年 / 6卷 / 26期
基金：
中国国家自然科学基金;
关键词：
microRNA-153; Nrf-2; GPx1; radiosensitivity; glioma stem cells; CANCER-CELLS; OXIDATIVE STRESS; GLUTATHIONE-PEROXIDASE; STEM/PROGENITOR CELLS; ANTIOXIDANT RESPONSE; IONIZING-RADIATION; THERAPEUTIC TARGET; CLINICAL-RELEVANCE; NRF2; EXPRESSION; IN-VITRO;
D O I：
10.18632/oncotarget.4292
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Glioma stem cells (GSCs) exhibit stem cell properties and high resistance to radiotherapy. The main aim of our study was to determine the roles of ROS in radioresistance and stemness of GSCs. We found that microRNA (miR)-153 was down-regulated and its target gene nuclear factor-erythroid 2-related factor-2 (Nrf-2) was up-regulated in GSCs compared with that of non-GSCs glioma cells. The enhanced Nrf-2 expression increased glutathione peroxidase 1 (GPx1) transcription and decreased ROS level leading to radioresistance of GSCs. MiR-153 overexpression resulted in increased ROS production and radiosensitization of GSCs. Moreover, miR-153 overexpression led to decreased neurosphere formation capacity and stem cell marker expression, and induced differentiation through ROS-mediated activation of p38 MAPK in GSCs. Nrf-2 overexpression rescued the decreased stemness and radioresistance resulting from miR-153 overexpression in GSCs. In addition, miR-153 overexpression reduced tumorigenic capacity of GSCs and increased survival in mice bearing human GSCs. These findings demonstrated that miR-153 overexpression decreased radioresistance and stemness of GSCs through targeting Nrf-2/GPx1/ROS pathway.
引用
收藏
页码：22006 / 22027
页数：22
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