microRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling

被引:154
作者
Lee, Kyung Min
Choi, Eun Jung
Kim, In Ah [1 ,2 ]
机构
[1] Seoul Natl Univ, Dept Radiat Oncol, Bundang Hosp, Med Res Inst, Songnam 463707, Kyeonggido, South Korea
[2] Seoul Natl Univ, Dept Radiat Oncol, Canc Res Inst, Songnam 463707, Kyeonggido, South Korea
基金
新加坡国家研究基金会;
关键词
microRNA-7; EGFR; PI3K; Akt; Radiosensitivity; GROWTH-FACTOR RECEPTOR; HUMAN TUMOR-CELLS; RAS; PATHWAY;
D O I
10.1016/j.radonc.2011.05.050
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Many microRNAs (miRNAs) play crucial roles in regulating expression of oncogenes or tumor suppressor genes. The epidermal growth factor receptor (EGFR) is frequently overexpressed in a wide range of solid tumors and is an important therapeutic target; however, the therapeutic outcome of currently available anti-EGFR agents is often limited due to diverse molecular resistance mechanisms. In this study, we evaluated the potential of targeting miRNA-7 for overcoming radio-resistance of cancer cells with activated EGFR-associated signaling. A panel of human cancer cell lines with increased EGFR-PI3K-Akt signaling was transfected with pre-miR-7 or control miRNA. Ectopic overexpression of miR-7 attenuated EGFR and Akt expression and radiosensitized SQ20B squamous cell carcinoma of the larynx, MDA-MB-468 breast cancer cells, A549 lung carcinoma cells, and U251 and U87 malignant glioma cells. In contrast, antisense-mediated inhibition of mature miR-7 expression led up-regulation of EGFR and its downstream effectors, and increased radio-resistance of U251 glioma cells. Overexpression of miR-7 prolonged radiation-induced gamma H2AX foci formation and downregulation of DNA-dependent protein kinases (DNA-PKcs). miR-7 may be a useful therapeutic target for overcoming the radio-resistance of human cancers with activated EGFR-P13K-AKT signaling. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 171-176
引用
收藏
页码:171 / 176
页数:6
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