Mechanism of apoptotic extracellular vesicles delivering LncRNA-XIST in drug resistance of glioma cells

Xue Jishan; Zhao Yuanyuan; Qiu Hao; Nuerjiang Ayixita; Liu Zheng; Du Peng

doi:10.13406/j.cnki.cyxb.003840

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Mechanism of apoptotic extracellular vesicles delivering LncRNA-XIST in drug resistance of glioma cells

Frontiers in brain science and neuropsychiatric disorders | 更新时间：2025-10-22

- Mechanism of apoptotic extracellular vesicles delivering LncRNA-XIST in drug resistance of glioma cells
- Journal of Chongqing Medical University Vol. 50, Issue 7, Pages: 931-939(2025)
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003840
  CLC： R739.41
- Received：30 January 2025，
  
  Revised：2025-03-19，
  
  Accepted：25 March 2025，
  
  Published：28 July 2025
- 稿件说明：
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薛箕山,赵媛媛,邱浩,等.凋亡外囊泡传递LncRNA-XIST在胶质瘤细胞耐药性作用机制研究[J].重庆医科大学学报,2025,50(7):931-939.

Xue Jishan,Zhao Yuanyuan,Qiu Hao,et al.Mechanism of apoptotic extracellular vesicles delivering LncRNA-XIST in drug resistance of glioma cells[J].Journal of Chongqing Medical University,2025,50(7):931-939.
薛箕山,赵媛媛,邱浩,等.凋亡外囊泡传递LncRNA-XIST在胶质瘤细胞耐药性作用机制研究[J].重庆医科大学学报,2025,50(7):931-939. DOI： 10.13406/j.cnki.cyxb.003840.

Xue Jishan,Zhao Yuanyuan,Qiu Hao,et al.Mechanism of apoptotic extracellular vesicles delivering LncRNA-XIST in drug resistance of glioma cells[J].Journal of Chongqing Medical University,2025,50(7):931-939. DOI： 10.13406/j.cnki.cyxb.003840.

摘要

目的

探讨胶质瘤细胞来源的凋亡外囊泡（apoptotic cell-derived extracellular vesicles，apoEVs）对胶质瘤肿瘤发生和替莫唑胺（temozolomide，TMZ）耐药性的影响及作用机制。

方法

经提取的apoEVs经纳米颗粒跟踪分析和透射电子显微镜表征，并通过Western blot、流式细胞术、CCK-8实验、细胞克隆形成实验和Transwell实验等方法评估其对细胞增殖、迁移、侵袭及凋亡的影响。

结果

apoEVs促进胶质瘤细胞的TMZ耐药性，显著提高TMZ半数抑制浓度（IC50）（

=9.326，

=0.001），抑制细胞凋亡，并通过外泌体抑制剂GW4869逆转该效应。

apoEVs促进胶质瘤细胞的迁移和侵袭，增加波形蛋白（Vimentin）和Twist蛋白的表达（

=8.762，

=0.002和

=7.941，

=0.004），抑制裂解型半胱氨酸天冬氨酸蛋白酶-3（leaved-Caspase-3）的表达（

=9.217，

=0.002）。进一步机制研究表明，apoEVs通过调控LncRNA-XIST/miR-29c/O6-甲基鸟嘌呤-DNA甲基转移酶（O6-methylguanine-DNA methyltransferase，MGMT）轴，影响胶质瘤细胞对TMZ的耐药性。沉默LncRNA-XIST降低MGMT表达、增加miR-29c表达，从而增强TMZ敏感性，抑制细胞迁移和侵袭。

结论

胶质瘤细胞来源的凋亡外囊泡通过传递LncRNA-XIST调节miR-29c/MGMT轴从而促进胶质瘤恶性进展和替莫唑胺耐药。

Abstract

Objective

To investigate the effect of glioma cell-derived apoptotic extracellular vesicles（apoEVs） on glioma tumorigenesis 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（

=9.326，

=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（

=8.762，

=0.002；

=7.941，

=0.004），and inhibited the expression of cleaved caspase-3（

=9.217，

=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 sen

sitivity to TMZ and inhibiting cell migration and invasion.

Conclusion

Glioma cell-derived apoEVs promote the malignant progression and temozolomide resistance of glioma by delivering LncRNA-XIST to regulate the miR-29c/MGMT axis.

关键词

Keywords

references

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