miR-374a Inhibitor Enhances Etoposide-Induced Cytotoxicity Against Glioma Cells Through Upregulation of FOXO1

Abstract

Glioma is a commonly diagnosed brain tumor that shows high mortality rate. Despite the great advancement of cancer therapy in recent years, chemotherapy is still an important approach for treatment of glioma. However, long-term chemotherapy usually causes serious side effects or complications. It is desirable to take strategies to enhance the efficacy of current chemotherapy. In the present study, we observed obvious upregulation of miR-374a in glioma cells. More importantly, we found that knockdown of miR-374a was able to enhance the etoposide-induced cytotoxicity against glioma cells. Mechanically, we demonstrated that FOXO1 was the target of miR-374a in glioma. Treatment with miR-374a inhibitor induced overexpression of FOXO1, and thus promoted the expression of Bim and Noxa. Since Bim and Noxa act as key proapoptotic proteins in mitochondrial apoptosis, miR-374a inhibitor was able to enhance the etoposide-induced apoptosis pathway in glioma.