Mechanism of apoptotic extracellular vesicles delivering LncRNA-XIST in drug resistance of glioma cells
10.13406/j.cnki.cyxb.003840
- VernacularTitle:凋亡外囊泡传递LncRNA-XIST在胶质瘤细胞耐药性作用机制研究
- Author:
Jishan XUE
1
;
Yuanyuan ZHAO
;
Hao QIU
;
Ayixita NUERJIANG
;
Zheng LIU
;
Peng DU
Author Information
1. 新疆维吾尔自治区新疆医科大学第二附属医院神经外科,乌鲁木齐 830000
- Keywords:
glioma;
apoptotic extracellular vesicles;
long non-coding RNA X-inactive specific transcript;
epithelial-mesenchymal transition;
miR-29c/O6-methylguanine-DNA methyltransferase axis
- From:
Journal of Chongqing Medical University
2025;50(7):931-939
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of glioma cell-derived apoptotic extracellular vesicles(apoEVs)on glioma tumorigen-esis and temozolomide(TMZ)resistance and its mechanism.Methods:The extracted apoEVs were characterized using nanoparticle tracking analysis and transmission electron microscopy,and Western blot,flow cytometry,CCK-8 assay,colony formation assay,and Transwell assay were used to investigate the effect of apoEVs on cell proliferation,migration,invasion,and apoptosis.Results:ApoEVs promoted TMZ resistance in glioma cells,significantly increased the half-maximal inhibitory concentration of TMZ(t=9.326,P=0.001),and inhibited cell apoptosis,and this effect could be reversed by the exosome inhibitor GW4869.ApoEVs also promoted the migration and invasion of glioma cells,increased the expression of vimentin and Twist proteins(t=8.762,P=0.002;t=7.941,P=0.004),and inhibited the expression of cleaved caspase-3(t=9.217,P=0.002).Further studies showed that apoEVs affected TMZ resistance of glioma cells by regulating the LncRNA-XIST/miR-29c/O6-methylguanine-DNA methyltransferase(MGMT)axis.Silencing of LncRNA-XIST could reduce the expression of MGMT and increase the expression of miR-29c,thereby enhancing the sensitivity to TMZ and inhibiting cell migration and invasion.Conclusion:Glioma cell-derived apoEVs promote the malignant progression and temo-zolomide resistance of glioma by delivering LncRNA-XIST to regulate the miR-29c/MGMT axis.
