Background

Glioma is a primary intracranial malignancy with poor prognosis, of which the pathogenesis remains to be elucidated. Therein, the aim of this study is to discuss the impacts of lncRNA plasmacytoma variant translocation 1 (PVT1)/microRNA-128−1-5p (miR-128−1-5p)/polypyrimidine tract-binding protein 1 (PTBP1) axis on the biological characteristics of glioma cells.

Methods

Glioma tissue samples (72 cases) and normal brain tissue samples (35 cases) were harvested. The expression of PVT1, miR-128−1-5p and PTBP1 in glioma tissues and cells was detected. Glioma cells were transfected with sh-PVT1, miR-128−1-5p mimics or miR-128−1-5p inhibitors to verify the impacts of PVT1 and miR-128−1-5p on DNA damage, cell colony formation, invasion, proliferation, migration and apoptosis of glioma U87 and U251 cells. The growth of transplanted tumor was tested by tumor xenograft in nude mice. The combination of PVT1 and miR-128−1-5p and the targeting relationship between miR-128−1-5p and PTBP1 were verified.

Results

PVT1 and PTBP1 expression was enhanced and miR-128−1-5p expression was degraded in glioma tissues and cells. Overexpressed miR-128−1-5p and lowly-expressed PVT1 promoted DNA damage, suppressed colony formation, invasion, proliferation and migration as well as boosted apoptosis of U251 and U87 cells. Up-regulating miR-128−1-5p and down-regulating PVT1 reduced transplanted tumor volume and weight of glioma in mice. Low expression miR-128−1-5p reversed the effect of low expression PVT1 on the biological characteristics of glioma cells. PVT1 specifically bound to miR-128−1-5p and PTBP1 was the target gene of miR-128−1-5p.

Conclusion

This study suggests that down-regulated PVT1 or up-regulated miR-128−1-5p boosts apoptosis and attenuates proliferation of glioma cells by inhibiting PTBP1 expression. This study is essential for finding new therapeutic targets for glioma.

中文翻译：

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低表达的 lncRNA PVT1 通过上调 microRNA-128-1-5p 和抑制 PTBP1 来抑制胶质瘤细胞的增殖并促进其凋亡。

背景

胶质瘤是一种预后较差的原发性颅内恶性肿瘤，其发病机制仍有待阐明。其中，本研究的目的是讨论 lncRNA 浆细胞瘤变异易位 1（PVT1）/microRNA-128-1-5p（miR-128-1-5p）/聚嘧啶束结合蛋白 1（PTBP1）轴对胶质瘤细胞的生物学特性。

方法

收集胶质瘤组织样本（72 例）和正常脑组织样本（35 例）。检测PVT1、miR-128-1-5p和PTBP1在胶质瘤组织和细胞中的表达。用 sh-PVT1、miR-128-1-5p 模拟物或 miR-128-1-5p 抑制剂转染胶质瘤细胞，以验证 PVT1 和 miR-128-1-5p 对 DNA 损伤、细胞集落形成、侵袭、胶质瘤 U87 和 U251 细胞的增殖、迁移和凋亡。通过裸鼠肿瘤异种移植测试移植肿瘤的生长。验证了 PVT1 与 miR-128-1-5p 的组合以及 miR-128-1-5p 与 PTBP1 之间的靶向关系。

结果

胶质瘤组织和细胞中PVT1和PTBP1表达增强，miR-128-1-5p表达降低。过表达的 miR-128-1-5p 和低表达的 PVT1 促进 DNA 损伤，抑制集落形成、侵袭、增殖和迁移，并促进 U251 和 U87 细胞的凋亡。上调 miR-128-1-5p 和下调 PVT1 可减少小鼠移植的肿瘤体积和神经胶质瘤的重量。低表达 miR-128-1-5p 逆转了低表达 PVT1 对胶质瘤细胞生物学特性的影响。PVT1 与 miR-128-1-5p 特异性结合，PTBP1 是 miR-128-1-5p 的靶基因。

结论

该研究表明，下调 PVT1 或上调 miR-128-1-5p 通过抑制 PTBP1 表达促进细胞凋亡并减弱神经胶质瘤细胞的增殖。这项研究对于寻找神经胶质瘤的新治疗靶点至关重要。