Folia Neuropathologica
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ISSN: 1641-4640
Folia Neuropathologica
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abstract:
Original paper

TREM2/DAP12 complex promotes proliferation and invasion of glioma cells via the PI3K-AKT signaling pathway

Zhitong Deng
1
,
Xingming Zhong
1
,
Yong Cai
1
,
Jianguo Yang
1
,
Yiqi Wang
1
,
Zhenhai Fei
1
,
Hua Gu
1
,
Tao Yang
1
,
Zhaohui Zhao
1

  1. Department of Neurosurgery, The First People’s Hospital of Huzhou (First Affiliated Hospital of Huzhou University), Huzhou, Zhejiang 313000, China
Folia Neuropathol 2025; 63
DOI: https://doi.org/10.5114/fn.2025.156003
Online publish date: 2025/11/27
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Introduction
Triggering receptor expressed on myeloid cells 2 (TREM2), part of the immunoglobulin superfamily, is implicated in various malignancies. However, its role in glioma formation remains unclear. Our study uncovered a potential mechanism involving TREM2.

Material and methods
The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets were utilized to assess the expression levels of TREM2 and DNAX-activating protein of 12 kDa (DAP12), explore their relationship, and evaluate their impact on patient prognosis. Western blotting was used to measure TREM2 expression in different glioma grades. Co-immunoprecipitation (Co-IP) was used to examine TREM2 and DAP12 interaction. Cell proliferation, invasion, and apoptosis were assessed via the cell proliferation test, cell invasion assay, and flow cytometry. An intracranial xenograft model was created by injecting tumor cells into nude mice. Mice injected with si-DAP12-transfected or non-transfected glioma cells were treated with 740Y-P, followed by survival analysis and immunohistochemistry.

Results
TREM2 and DAP12 were overexpressed in gliomas, with high levels associated with lower overall survival (p < 0.05 and p < 0.01). There was a strong positive correlation between TREM2 and DAP12 expression (p < 0.0001). TREM2 positively regulated DAP12, forming a complex that influenced glioma cell proliferation, apoptosis, and invasion (p < 0.05, p < 0.01, and p < 0.001). DAP12 knockdown significantly inhibited proliferation and invasion while promoting apoptosis of glioma cells, linked to the PI3K/AKT signaling pathway (p < 0.05 and p < 0.01). 740Y-P treatment counteracted the effects of DAP12 knockdown (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001). In vivo, DAP12 knockdown inhibited glioma tumorigenicity (p < 0.001).

Conclusions
TREM2 positively regulates DAP12 and forms a complex that impacts glioma development via the PI3K/AKT pathway. Targeting the TREM2/DAP12 complex presents a potential therapeutic approach for gliomas.

keywords:

glioma, triggering receptor expressed on myeloid cells 2, DNAX-activating protein of 12 kDa, phosphatidylino-sitol 3-kinase-protein kinase B signaling pathway

  
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