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YB-1 modulates the drug resistance of glioma cells by activation of MDM2/p53 pathway

Authors Tong H, Zhao K, Zhang J, Zhu J, Xiao J

Received 28 August 2018

Accepted for publication 22 November 2018

Published 14 January 2019 Volume 2019:13 Pages 317—326

DOI https://doi.org/10.2147/DDDT.S185514

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Qiongyu Guo


Hui Tong,1,* Kai Zhao,2,* Jingyu Zhang,3 Jinxin Zhu,4 Jianqi Xiao2

1Department of Neurosurgery, Linyi Central Hospital, Linyi, Shandong 276400, People’s Republic of China; 2Department of Neurosurgery, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161005, People’s Republic of China; 3Department of Internal Medicine, Jiangpu District Health Center of Huai’an, Huai’an, Jiangsu, 223001, People’s Republic of China; 4Department of Neurosurgery, Lianshui County People’s Hospital, Huai’an, Jiangsu 223400, People’s Republic of China

*These authors contributed equally to this work

Background: Y-box-binding protein-1 (YB-1) is aberrantly expressed in a variety of cancers. However, the biological functional role of YB-1 in glioma is not yet clear.
Methods: The expression of MDM2 and YB-1 was analyzed by real time PCR. Overexpression and knockdown of YB-1 in glioma cells were created by transfection of pcDNA-YB-1 and siRNA against YB-1, respectively. Cell viability was performed by CCK8 assay.
Results: Our findings showed that glioma tissues had higher expressions of YB-1 than that in cancer-free tissues in 54 glioma patients, which were also positively correlated with Murine MDM2 expression. Overexpression of YB-1 or MDM2 renders a drug resistance feature in glioma cell exposed to temozolomide (TMZ), by directly targeting p53. Genetic or chemical inhibition of MDM2 significantly blocked YB-1-modulated response of glioma cells to TMZ. Moreover, inhibition of YB-1 or MDM2 reduced glioma cells metastasis and mortality in mice.
Conclusion: YB-1 facilitates the resistance of glioma cells to TMZ by direct activation of MDM2/p53 signaling and represents a promising molecular target for glioma treatment.

Keywords: glioma, p53, Murine double minute 2, Y-box binding protein-1, drug resistance, temozolomide

 

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