EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A

EMB 通过 MCT4/GPX3 轴驱动多形性胶质母细胞瘤进展:Ganxintriol A 的治疗性抑制

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作者:Bo Cheng #, Jing Liu #, Ling Gao, Ziwen Zhu, Yang Yang, Shangqi Liu, Xiaojin Wu

Background

Embigin (EMB) is a transmembrane glycoprotein highly expressed in glioblastoma multiforme (GBM), yet its role in GBM progression remains unclear. In this study, we investigate the function of intracellular EMB in promoting GBM progression and evaluate the effect of Ganxintriol A, a traditional Chinese herbal extract, in GBM treatment.

Conclusions

This study highlights EMB as an independent prognostic biomarker for GBM and reveals a novel mechanism by which EMB drives GBM progression. Additionally, Ganxintriol A is identified as a promising therapeutic candidate for GBM treatment.

Methods

Bioinformatics datasets were utilized to assess EMB expression and its prognostic value in GBM patients. In vitro experiments such as PCR、western blot,CCK8,transwell,wound healing,clone formation and flow cytometry assays were conducted to examine EMB's biological functions and underlying mechanisms in GBM cell lines. Additionally, we constructed a subcutaneous tumor model in nude mice and evaluated the effect of traditional Chinese medicine extract Ganxintriol A on the progression of GBM through in vivo and in vitro experiments.

Results

EMB is highly expressed in GBM and is associated with poor prognosis in GBM patients. EMB overexpression accelerated GBM progression, whereas EMB knockdown had the opposite effect. Further analysis revealed that EMB upregulated epithelial-mesenchymal transition (EMT) and glycolysis while maintaining glutathione (GSH) redox balance by inducing monocarboxylate transporter 4 (MCT4) and glutathione peroxidase 3 (GPX3) expression. Treatment with Ganxintriol A significantly downregulated EMB expression, effectively inhibiting GBM progression both in vitro and in vivo. Conclusions: This study highlights EMB as an independent prognostic biomarker for GBM and reveals a novel mechanism by which EMB drives GBM progression. Additionally, Ganxintriol A is identified as a promising therapeutic candidate for GBM treatment.

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