Department of Neurosurgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528300, Guangdong, China.
Department of Neurosurgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528300, Guangdong, China.
Brain Res Bull. 2020 Oct;163:1-13. doi: 10.1016/j.brainresbull.2020.06.006. Epub 2020 Jun 17.
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.
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.
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.
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.
脑胶质瘤是一种原发性颅内恶性肿瘤，预后较差，其发病机制尚不清楚。本研究旨在探讨长链非编码 RNA 浆细胞瘤变异易位 1（PVT1）/微小 RNA-128-1-5p（miR-128-1-5p）/多嘧啶 tract 结合蛋白 1（PTBP1）轴对脑胶质瘤细胞生物学特性的影响。
收集 72 例脑胶质瘤组织样本和 35 例正常脑组织样本。检测脑胶质瘤组织和细胞中 PVT1、miR-128-1-5p 和 PTBP1 的表达。转染 sh-PVT1、miR-128-1-5p 模拟物或 miR-128-1-5p 抑制剂验证 PVT1 和 miR-128-1-5p 对 U87 和 U251 细胞 DNA 损伤、细胞集落形成、侵袭、增殖、迁移和凋亡的影响。通过裸鼠移植瘤实验检测移植瘤的生长。验证 PVT1 和 miR-128-1-5p 的结合及 miR-128-1-5p 与 PTBP1 的靶向关系。
脑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 miR-128-1-5p 和低表达 PVT1 促进 U251 和 U87 细胞的 DNA 损伤，抑制集落形成、侵袭、增殖和迁移，促进细胞凋亡。上调 miR-128-1-5p 和下调 PVT1 可降低裸鼠移植瘤的体积和重量。低表达 miR-128-1-5p 逆转了低表达 PVT1 对脑胶质瘤细胞生物学特性的影响。PVT1 特异性结合 miR-128-1-5p，PTBP1 是 miR-128-1-5p 的靶基因。
本研究表明，下调 PVT1 或上调 miR-128-1-5p 通过抑制 PTBP1 表达促进脑胶质瘤细胞凋亡，抑制增殖。本研究为寻找脑胶质瘤新的治疗靶点提供了依据。
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