Nur77 knock-down suppresses glioma by regulating CXCR4
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Department of Neurosurgery, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China
Department of Neurosurgery, Suqian People’s Hospital Affiliated to Xuzhou Medical University, Nanjing Drum Tower Hospital Group, Suqian, Jingsu, China
Submission date: 2020-01-15
Final revision date: 2020-04-11
Acceptance date: 2020-04-15
Online publication date: 2020-05-30
The aim of this study is to explain the effects and mechanisms of Nur77 in glioma development.

Material and methods:
Nur77 protein and gene expression were measured by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) in tissues from glioma and craniocerebral injury patients. The patients were divided into two groups according to median Nur77 gene expression and the correlations between clinical pathology, progression-free survival (PFS), overall survival (OS), and Nur77 gene expression were analysed. U257 and U87 cells were employed to assess the effects of Nur77 in cancer cell development by MTT, flow cytometry, and transwell and wound healing assays. Relative protein and gene expression were evaluated by Western blot assay and RT-qPCR, and PI3K nuclear volumes were evaluated by cellular immunofluorescence to explain the relevant mechanisms.

Compared with that in normal tissues, Nur77 protein and gene expression in glioma tissues was significantly up-regulated (p < 0.01); this up-regulation increased with increasing tumour stage (p < 0.01). Compared with the high Nur77 expression group, the low Nur expression group showed significantly improved PFS and OS (both p < 0.01). Nur77 gene expression appeared to be closely correlated with clinical pathology. In vitro studies of si-Nur77 transfection revealed a significant reduction in the cell viability of the si-Nur77 group, with increasing apoptosis rate (p < 0.001). Nur77 knock-down resulted in significant downregulation of cell invasion and wound healing rates in the si-Nur77 group (p < 0.01), with remarkable reductions in CXCR4 and PI3K.

Nur77 is an important oncogene in glioma, and Nur77 expression is closely correlated with glioma clinical pathology, PFS, and OS. Nur77 knock-down exerts inhibitory effects on glioma by regulating CXCR4/PI3K.