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Tumor Biology
Published in: Tumor Biology 7/2014

01-07-2014 | Research Article

miR-125b inhibitor enhance the chemosensitivity of glioblastoma stem cells to temozolomide by targeting Bak1

Authors: Jian Chen, Xingli Fu, Yi Wan, Zhimin Wang, Dongyi Jiang, Lei Shi

Published in: Tumor Biology | Issue 7/2014

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Abstract

Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly with a high frequency. Glioblastoma stem cells (GSCs) causing resistance to drug therapy were considered to be one of key factors. The mechanisms underlying GSCs resistance to TMZ are not fully understood. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. Previous study showed that miR-125b was necessary for GSCs fission and for making stem cells insensitive to chemotherapy. Thus, exploring the functions and mechanisms of miR-125b action on TMZ-treated GSCs would be valuable. In this study, we found that miR-125b was up-regulated in TMZ-resistant cells, inhibition of which caused a marked increase of TMZ-induced cytotoxicity and apoptosis and a subsequent decrease in the resistance to TMZ in GSCs. Moreover, we demonstrated that the pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) was a direct target of miR-125b. Down-regulation of Bak1 inhibited TMZ-induced apoptosis and led to an increased resistance to TMZ. Restoring Bak1 expression recovered TMZ sensitivity on GSCs. Taken together; our data strongly support an important role for miR-125b on conferring TMZ resistance through targeting Bak1 expression.
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Metadata
Title
miR-125b inhibitor enhance the chemosensitivity of glioblastoma stem cells to temozolomide by targeting Bak1
Authors
Jian Chen
Xingli Fu
Yi Wan
Zhimin Wang
Dongyi Jiang
Lei Shi
Publication date
01-07-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-1821-4

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