MicroRNA-101 reverses temozolomide resistance by inhibition of GSK3β in glioblastoma
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Tian Tian1,2,*, Ma Mingyi1,*, Xia Qiu3, Yang Qiu4
1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China
2Department of Neurology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China
3Department of Medicine, Shangqiu Medical School, Shangqiu 476000, Henan Province, People’s Republic of China
4Department of Clinical Medicine, Shaoyang Medical College, Shaoyang 422000, Hunan Province, People’s Republic of China
*These authors have contributed equally to this work
Tian Tian, email: firstname.lastname@example.org
Keywords: glioblastoma, temozolomide, chemoresistance, microRNA, prognosis
Received: September 07, 2016 Accepted: October 14, 2016 Published: October 25, 2016
Glioblastoma multiforme (GBM) is a chemotherapy-resistant brain tumor with limited treatment options. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug currently employed in GBM. Although it is currently the most promising chemotherapy for GBM, resistance to TMZ is also common and accounts for many treatment failures. Therefore, understanding the underlying mechanisms that generate resistance is essential to develop more effective chemotherapies. Here, we show that microRNA-101 (miR-101) was significantly downregulated in TMZ-resistant GBM cells and human specimens. Instead, over-expression of miR-101 could sensitize resistant GBM cells to TMZ through downregulation of glycogen synthase kinase 3β (GSK3β). Moreover, we found that GSK3β inhibition could enhance TMZ effect through repression of MGMT via promoter methylation. Importantly, decreased expression of miR-101 is related to poor prognosis in patients with GBM, suggesting its potential role as a new prognostic marker in GBM. In conclusion, our study demonstrates that miR-101 can reverse TMZ resistance by inhibition of GSK3β in GBM, thus offer a novel and powerful strategy for GBM therapy.
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