Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma.
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.
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xiao-Qiang
XQ
Wang
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Bang-Bao
BB
Tao
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Bin
B
Li
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xu-Hui
XH
Wang
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wen-Chuan
WC
Zhang
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Liang
L
Wan
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xu-Ming
XM
Hua
Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shi-Ting
ST
Li
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009857:Oncogenes / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
TREM2; chemokine pathway; glioma; invasion; proliferation