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PVT1通过负向调控miR-186影响胶质瘤微血管内皮细胞的生长。

PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186.

作者信息

Ma Yawen, Wang Ping, Xue Yixue, Qu Chengbin, Zheng Jian, Liu Xiaobai, Ma Jun, Liu Yunhui

机构信息

1 Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.

2 Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, People's Republic of China.

出版信息

Tumour Biol. 2017 Mar;39(3):1010428317694326. doi: 10.1177/1010428317694326.

Abstract

Vigorous angiogenesis is one of the reasons for the poor prognosis of glioma. A number of studies have shown that long non-coding RNA can affect a variety of biological behaviors of tumors. However, the influence of long non-coding RNAs on glioma vascular endothelial cells remains unclear. To simulate the glioma microenvironment, we applied glioma-conditioned medium to human cerebral microvascular endothelial cells. The long non-coding RNA PVT1 was found to be highly expressed in glioma vascular endothelial cells. Cell Counting Kit-8, migration, and tube formation assays showed that PVT1 overexpression promoted glioma vascular endothelial cells proliferation, migration, and angiogenesis. We also found that PVT1 overexpression upregulated the expression of the autophagy-related proteins Atg7 and Beclin1, which induced protective autophagy. Bioinformatics software and dual-luciferase system analysis confirmed that PVT1 acts by targeting miR-186. In addition, our study showed that miR-186 could target the 3' untranslated region of Atg7 and Beclin1 to decrease their expression levels, thereby inhibiting glioma-conditioned human cerebral microvascular endothelial cell autophagy. In conclusion, PVT1 overexpression increased the expression of Atg7 and Beclin1 by targeting miR-186, which induced protective autophagy, thus promoting glioma vascular endothelial cell proliferation, migration, and angiogenesis. Therefore, PVT1 and miR-186 can provide new therapeutic targets for future anti-angiogenic treatment of glioma.

摘要

活跃的血管生成是胶质瘤预后不良的原因之一。多项研究表明,长链非编码RNA可影响肿瘤的多种生物学行为。然而,长链非编码RNA对胶质瘤血管内皮细胞的影响仍不清楚。为了模拟胶质瘤微环境,我们将胶质瘤条件培养基应用于人类脑微血管内皮细胞。发现长链非编码RNA PVT1在胶质瘤血管内皮细胞中高表达。细胞计数试剂盒-8、迁移和管形成试验表明,PVT1过表达促进了胶质瘤血管内皮细胞的增殖、迁移和血管生成。我们还发现,PVT1过表达上调了自噬相关蛋白Atg7和Beclin1的表达,从而诱导了保护性自噬。生物信息学软件和双荧光素酶系统分析证实,PVT1通过靶向miR-186发挥作用。此外,我们的研究表明,miR-186可靶向Atg7和Beclin1的3'非翻译区以降低其表达水平,从而抑制胶质瘤条件下的人类脑微血管内皮细胞自噬。总之,PVT1过表达通过靶向miR-186增加了Atg7和Beclin1的表达,诱导了保护性自噬,从而促进了胶质瘤血管内皮细胞的增殖、迁移和血管生成。因此,PVT1和miR-186可为未来胶质瘤的抗血管生成治疗提供新的治疗靶点。

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