Abstract：
: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 α (PPARα) and that miR-21 regulates EGFR/AKT signaling through VHL/β-catenin and the PPARα/AP-1 axis. Further, the expression of miR-21 is regulated by EGFR via the activation of β-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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Zhang KL,Han L,Chen LY,Shi ZD,Yang M,Ren Y,Chen LC,Zhang JX,Pu PY,Kang CSdoi
10.1016/j.canlet.2013.08.043subject
Has Abstractpub_date
2014-01-01 00:00:00pages
139-49issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(13)00640-Xjournal_volume
342pub_type
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