长链非编码 RNA LINC01426 通过 PI3K/AKT 信号通路促进脑胶质瘤的进展，并作为一种预后生物标志物。
Long noncoding RNA LINC01426 promotes glioma progression through PI3K/AKT signaling pathway and serves as a prognostic biomarker.
机构信息
Department of Neurosurgery, Jining No. 1 People's Hospital, Jining, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Oct;22(19):6358-6368. doi: 10.26355/eurrev_201810_16047.
OBJECTIVE
Growing evidence indicated that long intergenic non-protein coding RNA 1426 (LINC01426) played important roles in tumor initiation and progression. However, little was known about the expression pattern and biological function of LINC01426 in glioma. Here, we aimed to determine its expression pattern, clinicopathological significance, and biological roles in glioma.
PATIENTS AND METHODS
The Cancer Genome Atlas (TCGA) data was used to screen abnormally expressed lncRNAs in glioma. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed to detect the expression of LINC01426 in both glioma tissues and cell lines. Then, the associations between LINC01426 expression levels and various clinicopathologic characteristics and the clinical prognosis of patients with glioma were analyzed. The loss-of-function assay was performed to explore the effect of LINC01426 on glioma proliferation, metastasis, and apoptosis. Western blotting was performed to assess the protein expression levels.
RESULTS
We identified a differentially expressed novel oncogenic lncRNA termed as LINC01426 by TCGA. Subsequent RT-PCT indicated that LINC01426 expression was significantly up-regulated in both glioma tissues and cell lines. Increased LINC01426 expression was negatively correlated with WHO grade and KPS score. Furthermore, LINC01426 could serve as an independent predictor for overall survival in glioma. In vitro assay revealed that knockdown of LINC01426 suppressed glioma cells proliferation, migration and invasion, and induced apoptosis. Mechanistic investigation showed that LINC01426 exhibited its tumor promoter role by modulating PI3K/Akt signaling pathway in glioma.
CONCLUSIONS
The present study indicated that LINC01426 functioned as a tumor promoter and it might be a potential biomarker and therapeutic target in glioma.
目的
越来越多的证据表明，长链非编码 RNA 1426（LINC01426）在肿瘤的发生和发展中发挥着重要作用。然而，关于 LINC01426 在神经胶质瘤中的表达模式和生物学功能知之甚少。本研究旨在确定其在神经胶质瘤中的表达模式、临床病理意义和生物学作用。
方法
利用癌症基因组图谱（TCGA）数据筛选神经胶质瘤中异常表达的 lncRNA。采用逆转录-聚合酶链反应（RT-PCR）检测 LINC01426 在神经胶质瘤组织和细胞系中的表达。然后，分析 LINC01426 表达水平与各种临床病理特征和神经胶质瘤患者临床预后的关系。采用基因敲低实验探讨 LINC01426 对神经胶质瘤增殖、转移和凋亡的影响。采用 Western blot 检测蛋白表达水平。
结果
我们通过 TCGA 鉴定出一种差异表达的新型致癌 lncRNA，称为 LINC01426。随后的 RT-PCR 结果表明，LINC01426 在神经胶质瘤组织和细胞系中表达显著上调。LINC01426 的高表达与 WHO 分级和 KPS 评分呈负相关。此外，LINC01426 可作为神经胶质瘤患者总生存期的独立预测因子。体外实验表明，下调 LINC01426 抑制神经胶质瘤细胞增殖、迁移和侵袭，并诱导细胞凋亡。机制研究表明，LINC01426 通过调节神经胶质瘤中的 PI3K/Akt 信号通路发挥其肿瘤促进作用。
结论
本研究表明，LINC01426 具有肿瘤促进作用，可能是神经胶质瘤的潜在生物标志物和治疗靶点。
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