Targeting EHMT2 inhibition in glioblastoma: effects on tumor progression and STAT3 signaling

Euchromatic Histone Lysine Methyltransferase 2 (EHMT2), also known as G9a, is a key member of the SET domain family and plays a critical role in the initiation and progression of malignant tumors, including glioma, especially glioblastoma (GBM). Its involvement in various cancer types suggests its potential as a therapeutic target. This study aims to investigate the effects of the targeted EHMT2 inhibitor BIX-01294 on the malignant phenotypes of GBM cells and to explore the underlying molecular mechanisms.

In this study, we analyzed the expression levels of EHMT2 in various tumors and analyzed the expression of EHMT2 in different subtypes of glioma and GBM. The targeted EHMT2 inhibitor BIX-01294 was employed to investigate its effects on the malignant phenotype of GBM cells. The cellular processes of proliferation, invasion, and self-renewal were assessed, alongside the expression of proteins associated with these processes. Additionally, bioinformatics analysis was conducted to explore the relationship between EHMT2 and various biological processes in GBM.

EHMT2 is highly expressed in gliomas and significantly expressed in GBM. Among the four subtypes of GBM, the classical and preneuronal subtypes have higher expression. The results revealed that BIX-01294 significantly inhibited GBM cells proliferation, invasion, and self-renewal. Furthermore, the expression of proteins linked to invasion and proliferation was notably reduced. Bioinformatics analysis showed that EHMT2 is closely associated with multiple biological processes in glioma and might regulate the signal transducer and activator of transcription 3 (STAT3) signaling pathway through NFκB.

These findings suggest that targeting EHMT2 with BIX-01294 could provide anti-tumor effects by disrupting key signaling pathways, including STAT3. This approach offers a promising new strategy for the clinical treatment of GBM.