Blockage of a miR-21/EGFR regulatory feedback loop augments anti-EGFR therapy in glioblastomas

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• 作者：Kai-liang Zhang ; Lei Han ; Lu-yue Chen ; Zhen-dong Shi ; Ming Yang ; Yu Ren ; Ling-chao Chen ; Jun-xia Zhang ; Pei-yu Pu ; Chun-sheng Kang
• 关键词：Glioblastoma ; EGFR ; Feedback loop ; miR-21
• 刊名：Cancer Letters
• 出版年：1 January, 2014
• 年：2014
• 卷：342
• 期：1
• 页码：139-149
• 全文大小：2871 K

文摘

Epidermal growth factor receptors (EGFR) expression is frequently amplified in human glioblastoma cells. Nimotuzumab, a monoclonal antibody (mAb) against EGFR, has been used globally in clinics as an anti-cancer agent. It is largely unknown whether the blockade of miR-21, a microRNA that is upregulated in glioma cells, could amplify the effects of nimotuzumab. Herein, we have demonstrated that miR-21 directly targets von Hippel-Lindau (VHL) and peroxisome-proliferator-activated receptor 伪 (PPAR伪) and that miR-21 regulates EGFR/AKT signaling through VHL/尾-catenin and the PPAR伪/AP-1 axis. Further, the expression of miR-21 is regulated by EGFR via the activation of 尾-catenin and AP-1. These data indicate that a feedback loop exists between miR-21 and EGFR. We also show that the combination of nimotuzumab and an inhibitor of miR-21 is superior to single-agent therapy. These results clarify a novel association between miR-21 and EGFR in the regulation of cancer cell progression.