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.