TLR2 通过增强自噬促进人神经胶质瘤的发生发展。

TLR2 promotes development and progression of human glioma via enhancing autophagy.

机构信息

Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou 256603, China.

Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100000, China.

出版信息

Gene. 2019 Jun 5;700:52-59. doi: 10.1016/j.gene.2019.02.084. Epub 2019 Mar 19.

DOI:10.1016/j.gene.2019.02.084

PMID:30898699

Abstract

OBJECTIVE

In this study, we aim to evaluate Toll-like receptor 2 (TLR2) expression in human glioma tumors and the correlation between its expression with degrees of malignancy and autophagy, development of tumors.

METHOD

Immunohistochemistry and Western blot were carried out to determine the expression of LC3, Beclin1 and TLR2 in 74 glioma specimens. We analyzed the prognosis of 551 glioma patients through the Cancer Genome Atlas (TCGA). To determine the effect of TLR2 in glioma, we manipulated TLR2 expression using TLR2 plasmid transfer technique in U87 human glioma cell.

RESULTS

TLR2 expression in high-grade was significantly higher than that in low-grade glioma group (P < 0.05). TLR2 was positively correlated with tumor grade (P < 0.05). Spearman correlation showed that the expression of TLR2 was positively correlated with the numbers of LC3 and Beclin1 (P < 0.05). The patients with high TLR2 expression had a poorer outcome compared with the patients with low TLR2 in low-grade glioma (P < 0.05). TLR2 overexpression enhances glioma cell activity and accelerates cell cycle progression. In addition, treatment with TLR2 overexpression increases the conversion rate of LC3-I to LC3-II and enhances the level of phosphorylated p38.

CONCLUSION

TLR2 promotes development and progression of human glioma via enhancing autophagy.

摘要

目的

本研究旨在评估 Toll 样受体 2（TLR2）在人胶质瘤肿瘤中的表达及其与恶性程度和自噬、肿瘤发展的相关性。

方法

采用免疫组织化学和 Western blot 法检测 74 例胶质瘤标本中 LC3、Beclin1 和 TLR2 的表达。通过癌症基因组图谱（TCGA）分析 551 例胶质瘤患者的预后。为了确定 TLR2 在胶质瘤中的作用，我们使用 TLR2 质粒转染技术在 U87 人胶质瘤细胞中操纵 TLR2 的表达。

结果

高级别胶质瘤中 TLR2 的表达明显高于低级别胶质瘤组（P<0.05）。TLR2 与肿瘤分级呈正相关（P<0.05）。Spearman 相关性分析显示，TLR2 的表达与 LC3 和 Beclin1 的数量呈正相关（P<0.05）。与低级别胶质瘤中 TLR2 低表达的患者相比，TLR2 高表达的患者预后较差（P<0.05）。TLR2 过表达增强了胶质瘤细胞的活性并加速了细胞周期进程。此外，TLR2 过表达的治疗增加了 LC3-I 向 LC3-II 的转化率，并增强了磷酸化 p38 的水平。