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Article Abstract
Background: Glioma, the most common primary tumour of the nervous system. The prognosis of glioma often depends on WHO grade. EPB41L3 (4.1B/Dal-1) is involved in the development and progression of multiple tumours. However, the role of EPB41L3 in glioma remains to be elucidated.
Methods: EPB41L3 mRNA expression in glioma was analysed in multiple datasets. Overall survival (OS) and progression-free interval (PFI) were analysed in patients who were divided into high and low EPB41L3 expression groups. The correlation between EPB41L3 expression and methylation was analysed and subsequently validated in glioma cells. Whether EPB41L3 impacts the tumour immune microenvironment (TIME) was investigated by evaluating its association with immune function, immune cells, and immune checkpoints. Additionally, EPB41L3's tumor-suppressive role was confirmed through functional assays including cell proliferation, invasion, flow cytometry-based cell cycle, and apoptosis analysis.
Results: EPB41L3 expression was lower in glioma than in normal tissues. The immunohistochemical results showed that EPB41L3 expression gradually decreased with increasing WHO grade. Patients with glioma had longer OS and PFI in the high EPB41L3 expression group. EPB41L3 expression was negatively correlated with methylation, and most methylation sites were associated with poor OS in glioma. In addition, EPB41L3 was associated with various immune functions, immune cells, and immune checkpoints. EPB41L3-overexpressing cells were generated by lentiviral transduction. CCK-8, colony formation, Transwell, and scratch assays showed that EPB41L3 inhibited glioma cell proliferation and migration. EPB41L3 inhibits glioma mainly through apoptosis induction. Cell cycle and apoptosis results showed that EPB41L3 could inhibit glioma through apoptosis.
Conclusion: EPB41L3 expression is lower and the methylation level is higher in glioma, which not only play roles in tumour suppression but also are related to prognosis and the tumour immune microenvironment. EPB41L3 can be used as a prognostic and therapeutic biomarker for glioma.
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