OncotargetOct 30, 2016

MicroRNA-101 may reverse chemotherapy resistance by blocking a key enzyme in brain cancer

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

MicroRNA-101 (miR-101) was significantly downregulated in TMZ-resistant glioblastoma multiforme (GBM) cells and human specimens.

Over-expression of miR-101 may sensitize resistant GBM cells to temozolomide (TMZ).
Downregulation of glycogen synthase kinase 3β (GSK3β) is associated with the sensitization of GBM cells to TMZ.
GSK3β inhibition could enhance the effectiveness of TMZ through repression of the MGMT gene via promoter methylation.
Decreased expression of miR-101 is related to poor prognosis in GBM patients, indicating its potential as a prognostic marker.
This suggests that targeting miR-101 could offer a novel strategy for overcoming TMZ resistance in GBM.

Simplified

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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MicroRNA-101 may reverse chemotherapy resistance by blocking a key enzyme in brain cancer

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