Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/36332
Title: MiR-181b sensitizes glioma cells to teniposide by targeting MDM2
Authors: Sun, YC
Wang, J
Guo, CC
Sai, K
Wang, J
Chen, FR
Yang, QY
Chen, YS
Wang, J
To, TSS 
Zhang, ZP
Mu, YG
Chen, ZP
Keywords: miR-181b
Teniposide
Glioma
Mouse double minute 2 homolog (MDM2)
Issue Date: 2014
Publisher: BioMed Central
Source: BMC cancer, 2014, v. 14, 611, p. 1-7 How to cite?
Journal: BMC cancer 
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.
URI: http://hdl.handle.net/10397/36332
ISSN: 1471-2407
DOI: 10.1186/1471-2407-14-611
Rights: © 2014 Sun et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.
The following publication Sun, Y. C., Wang, J., Guo, C. C., Sai, K., Wang, J., Chen, F. R., … Chen, Z. P. (2014). MiR-181b sensitizes glioma cells to teniposide by targeting MDM2. BMC Cancer, 14, 611, 1-7 is available at https://dx.doi.org/10.1186/1471-2407-14-611
Appears in Collections:Journal/Magazine Article

Files in This Item:
File Description SizeFormat 
Sun_Mir-181B_Sensitizes_Glioma.pdf927.7 kBAdobe PDFView/Open
Access
View full-text via PolyU eLinks SFX Query
Show full item record
PIRA download icon_1.1View/Download Contents

SCOPUSTM   
Citations

40
Last Week
1
Last month
Citations as of Apr 5, 2019

WEB OF SCIENCETM
Citations

36
Last Week
0
Last month
Citations as of Apr 4, 2019

Page view(s)

119
Last Week
0
Last month
Citations as of Oct 23, 2019

Download(s)

5
Citations as of Oct 23, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.