骨髓间充质干细胞来源的外泌体通过下调GFI1传递microRNA-142-3p干扰胶质瘤进展。

IF 2.9 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Discover. Oncology Pub Date : 2025-02-10 DOI:10.1007/s12672-025-01837-4
Huahui Chen, Lixiong Xue, Xiaolong Wang, Li Han, Xinmin Ding
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引用次数: 0

摘要

目的:胶质瘤的发病机制已被广泛探讨,而对外泌体microRNA-142-3p/独立生长因子-1(miR-142-3p/GFI1)轴在胶质瘤中的作用的理解仍处于初始阶段。因此,本研究旨在确定骨髓间充质干细胞衍生的外泌体(BMSCs-Exos)/miR-142-3p/GFI1轴在胶质瘤发展中的作用:方法:收集胶质瘤患者的癌组织和脑外伤手术患者的正常脑组织,测量组织和细胞中miR-142-3p和GFI1的表达。将携带 miR-142-3p 的 BMSCs 外泌体与胶质瘤细胞共培养,观察外泌体 miR-142-3p 对胶质瘤细胞侵袭、迁移和凋亡的影响。研究验证了 miR-142-3p 与 GFI1 的靶向关系。结果:miR-142-3p在胶质瘤组织和细胞中低表达,低表达与预后不良有关。外显子修饰的 miR-142-3p 可抑制胶质瘤细胞的迁移和侵袭,同时促进其凋亡。进一步研究发现,GFI1是miR-142-3p的直接靶标,而GFI1的重新表达中和了外泌体miR-142-3p的抑制作用:结论:外泌体miR-142-3p通过靶向GFI1抑制胶质瘤细胞的迁移和侵袭,并刺激细胞凋亡。
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Bone marrow mesenchymal stem cells-derived exosomes deliver microRNA-142-3p to disturb glioma progression by down-regulating GFI1.

Objective: The mechanism of glioma development has been extensively explored and comprehension of the exosomal microRNA-142-3p/growth factor independent-1 (miR-142-3p/GFI1) axis in glioma is still at an initial stage. Therein, the conducted work goes toward ascertaining the role of the bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos)/miR-142-3p/GFI1 axis in glioma development.

Methods: Cancer tissues from patients with glioma and normal brain tissues from those who underwent surgery for traumatic brain injury were collected. miR-142-3p and GFI1 expression in tissues and cells were measured. Exos derived from BMSCs carrying miR-142-3p were cocultured with glioma cells to observe the effects of exosomal miR-142-3p on glioma cell invasion, migration, and apoptosis. The targeting relationship of miR-142-3p and GFI1 was validated. A series of rescue assays were conducted to further investigate whether GFI1 is implicated in the exosomal miR-142-3p-mediated regulation of glioma cell invasion, migration, and apoptosis.

Results: miR-142-3p was low-expressed in glioma tissues and cells, and the low expression had an association with unwanted prognosis. Exos-shuttled miR-142-3p suppressed the migration and invasion, while promoting apoptosis of glioma cells. Further investigation revealed that GFI1 was a direct target of miR-142-3p, and re-expression of GFI1 neutralized the inhibitory effects of exosomal miR-142-3p.

Conclusion: Exosomal miR-142-3p suppressed glioma cell migration and invasion and stimulated apoptosis by targeting GFI1.

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来源期刊
Discover. Oncology
Discover. Oncology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.40
自引率
9.10%
发文量
122
审稿时长
5 weeks
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