Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma

胶质瘤 癌症研究 癌基因 癌变 小桶 细胞生长 细胞周期 基因敲除 生物 U87型 细胞凋亡 特雷姆2 肿瘤微环境 癌症 细胞 医学 PI3K/AKT/mTOR通路 下调和上调 脑瘤 蛋白激酶B 基因 基因表达 转录组 遗传学 髓样 髓系细胞
作者
Xiaoqiang Wang,Bangbao Tao,Bin Li,Xizhang Wang,Wenchuan Zhang,Liang Wan,Xuming Hua,Shiting Li
出处
期刊:Oncotarget [Impact Journals, LLC]
卷期号:7 (3): 2354-2366 被引量:44
标识
DOI:10.18632/oncotarget.6221
摘要

Gliomas are the most common and aggressive type of primary adult brain tumors. Although TREM2 mutation is reported to be related to Nasu-Hakola disease and Alzheimer's disease, little is known about the association between TREM2 and gliomas. Here, we reported that TREM2 was significantly overexpressed in glioma tissues compared with non-tumorous brain tissues. Furthermore, TREM2 expression was closely related to pathological grade and overall survival of patients with gliomas. Down-regulation of TREM2 in two glioma cell lines, U87 and U373, resulted in a significant reduction in cell proliferation, migration and invasion and a dramatic increase in S phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TREM2 expression inhibited U87 cell proliferation. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TREM2 was positive related to Kyoto Encyclopedia of Genes and Genomes (KEGG) apoptosis, Cromer metastasis and KEGG chemokine pathways, which was further validated by western blot in TREM2 knockdown glioma cells and indicated a possible mechanism underlying its effects on glioma. In summary, our study suggests that TREM2 may work as an oncogene and a new effective therapeutic target for glioma treatment.

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