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MicroRNA-101 reverses temozolomide resistance by inhibition of GSK3? in glioblastoma.


ABSTRACT: 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 3? (GSK3?). Moreover, we found that GSK3? 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 GSK3? in GBM, thus offer a novel and powerful strategy for GBM therapy.

SUBMITTER: Tian T 

PROVIDER: S-EPMC5346737 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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MicroRNA-101 reverses temozolomide resistance by inhibition of GSK3β in glioblastoma.

Tian Tian T   Mingyi Ma M   Qiu Xia X   Qiu Yang Y  

Oncotarget 20161101 48


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 m  ...[more]

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