长链非编码 RNA PVT1 通过下调 UPF1 促进神经胶质瘤的进展。

LncRNA PVT1 aggravates the progression of glioma via downregulating UPF1.

机构信息

Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):8956-8963. doi: 10.26355/eurrev_201910_19294.

DOI:10.26355/eurrev_201910_19294

PMID:31696483

Abstract

OBJECTIVE

To uncover the influence of plasmacytoma variant translocation 1 (PVT1) on aggravating the progression of glioma via downregulating UPF1.

PATIENTS AND METHODS

The relative levels of PVT1 and UPF1 in glioma tissues were determined. PVT1 level in glioma patients in stage I+II and stage III+IV, and either with metastasis or not was examined as well. The Kaplan-Meier curves were depicted for assessing the survival in glioma patients expressing a high and low level of PVT1. The regulatory effects of PVT1 and UPF1 on the proliferative and migratory abilities of U87 and LN229 cells were evaluated. The subcellular distributions of PVT1 and UPF1 were analyzed, and their interaction was investigated by performing RNA immunoprecipitation (RIP) assay. At last, the mRNA level of UPF1 was determined in U87 and LN229 cells overexpressing PVT1 treated with 50 μM α-amanitin.

RESULTS

PVT1 was upregulated in glioma tissues relative to controls. Its level was higher in glioma patients with advanced stage or accompanied by metastasis. The glioma patients with a high level of PVT1 suffered a worse prognosis. The overexpression of PVT1 accelerated proliferative and migratory abilities of U87 and LN229 cells. UPF1 was conversely downregulated in glioma patients. Its level was negatively correlated to that of PVT1. The overexpression of UPF1 attenuated the proliferative and migratory abilities of U87 and LN229 cells. Both PVT1 and UPF1 were mainly enriched in the cytoplasm. The interaction between PVT1 and UPF1 was identified in the RIP assay. PVT1 prolonged the half-life of UPF1 and inhibited its synthesis.

CONCLUSIONS

PVT1 accelerates the proliferative and migratory abilities of glioma via downregulating UPF1.

摘要

目的

通过下调 UPF1，揭示浆细胞瘤变异易位 1（PVT1）对加剧神经胶质瘤进展的影响。

方法

检测神经胶质瘤组织中 PVT1 和 UPF1 的相对水平。检查 I+II 期和 III+IV 期的神经胶质瘤患者，以及是否有转移的 PVT1 水平。通过绘制 Kaplan-Meier 曲线评估表达高水平和低水平 PVT1 的神经胶质瘤患者的生存情况。评估 PVT1 和 UPF1 对 U87 和 LN229 细胞增殖和迁移能力的调节作用。分析 PVT1 和 UPF1 的亚细胞分布，并通过 RNA 免疫沉淀（RIP）测定研究它们的相互作用。最后，在过表达 PVT1 的 U87 和 LN229 细胞中用 50μMα-鹅膏蕈碱处理后，测定 UPF1 的 mRNA 水平。

结果

与对照相比，PVT1 在神经胶质瘤组织中上调。晚期或伴有转移的神经胶质瘤患者 PVT1 水平较高。PVT1 水平较高的神经胶质瘤患者预后较差。PVT1 的过表达加速了 U87 和 LN229 细胞的增殖和迁移能力。相反，神经胶质瘤患者 UPF1 下调。其水平与 PVT1 呈负相关。UPF1 的过表达减弱了 U87 和 LN229 细胞的增殖和迁移能力。PVT1 和 UPF1 主要富集在细胞质中。在 RIP 测定中鉴定了 PVT1 和 UPF1 之间的相互作用。PVT1 延长了 UPF1 的半衰期并抑制其合成。