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

作者：Hui Tong, Kai Zhao, Jingyu Zhang, Jinxin Zhu, Jianqi Xiao · 发表于：Drug Design Development and Therapy · 年份：2019 · DOI：10.2147/dddt.s185514 · 被引用次数：39 · 研究领域：RNA Research and Splicing、Hippo pathway signaling and YAP/TAZ、Immune Cell Function and Interaction

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.