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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

MiR-181b sensitizes glioma cells to teniposide by targeting MDM2

Authors: Yan-chang Sun, Jing Wang, Cheng-cheng Guo, Ke Sai, Jian Wang, Fu-rong Chen, Qun-ying Yang, Yin-sheng Chen, Jie Wang, Tony Shing-shun To, Zong-ping Zhang, Yong-gao Mu, Zhong-ping Chen

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide.

Methods

MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells.

Results

Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3’-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b.

Conclusions

MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3’-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.
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Metadata
Title
MiR-181b sensitizes glioma cells to teniposide by targeting MDM2
Authors
Yan-chang Sun
Jing Wang
Cheng-cheng Guo
Ke Sai
Jian Wang
Fu-rong Chen
Qun-ying Yang
Yin-sheng Chen
Jie Wang
Tony Shing-shun To
Zong-ping Zhang
Yong-gao Mu
Zhong-ping Chen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-611

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