Circ_EPHB4 regulates temozolomide sensitivity in glioma cells through the miR-424-5p/Wnt3 axis.
10.12122/j.issn.1673-4254.2025.05.06
- Author:
Yuxiang LIAO
1
;
Jingping LIU
1
;
Bo LIU
1
;
Xiyun FEI
1
;
Chen JIN
1
Author Information
1. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- Keywords:
Wnt3;
chemoresistance;
circ_EPHB4;
glioma;
miR-424-5p
- MeSH:
MicroRNAs/genetics*;
Humans;
Temozolomide;
Glioma/genetics*;
Animals;
Mice, Nude;
Cell Line, Tumor;
Wnt3 Protein/metabolism*;
Mice;
Apoptosis;
RNA, Circular;
Drug Resistance, Neoplasm;
Brain Neoplasms/pathology*;
Signal Transduction
- From:
Journal of Southern Medical University
2025;45(5):942-953
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the mechanism by which circ_EPHB4 regulates temozolomide (TMZ) sensitivity of glioma cells through the miR-424-5p/Wnt3 signal axis.
METHODS:We detected the expression levels of circ_EPHB4, miR-424-5p and Wnt3 mRNA in glioma specimens from 25 patients with primary glioma and 25 patients experiencing relapse following temozolomide-based chemotherapy and in TMZ-sensitive and -resistant glioma A172 and SHG44 cells with circ_EPHB4 knockdown using qRT-PCR, and Wnt3 protein expression level was detected with Western blotting. Cell viability, colony-forming ability, and apoptosis of the cells with circ_EPHB4 knockdown were assessed, and the targeted regulation relationship between circ_EPHB4, miR-424-5p, and Wnt3 was verified by dual luciferase reporter assay and RNA immunoprecipitation (RIP) experiments. The effect of circ_EPHB4 knockdown on tumorigenesis of glioma cells was evaluated in subcutaneous tumor-bearing nude mouse models.
RESULTS:The expression of circ_EPHB4 was significantly increased in glioma tissues and cells as compared with normal neural tissues and astrocytes (P=0.014). In TMZ-resistant glioma cells, circ_EPHB4 knockdown resulted in an obvious reduction of IC50 value of TMZ, inhibited cell colony formation, and promoted cell apoptosis, and these effects were reversed by miR-424-5p knockdown. The expressions of miR-424-5p and circ_EPHB4 were negatively correlated in glioma tissues (P=0.011). MiR-424-5p knockdown also attenuated the effect of circ_EPHB4 knockdown on expressions of PCNA, P-gp, MRP1 and bax.
CONCLUSIONS:Circ_EPHB4 regulates Wnt3 expression through "sponge adsorption" of miR-424-5p, thereby modulating TMZ-resistant glioblastoma cell clonogenesis, apoptosis, and TMZ sensitivity, suggesting the potential of circ_EPHB4 as a therapeutic target for reversing drug resistance of gliomas.
