Peroxidasin promotes malignant progression by enhancing glycolytic metabolism in glioblastoma through the regulation of LDHA

Objectives: Aberrant glucose metabolism serves as a hallmark of glioblastoma (GBM). This study aimed to identify biomarkers linked with glycolysis in GBM, thereby providing a theoretical framework for its treatment.

Methods: We retrieved the gene expression profiles from the GSE 50161 dataset, screened differentially expressed genes (DEGs) and key modules through Weighted Gene Co-expression Network Analysis (WGCNA), and ultimately identified the critical gene via protein-protein interaction (PPI) networks, receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis. In addition, we employed multifaceted immunological, metabolic, and functional assays to experimentally elucidate the regulatory mechanisms of the critical gene within the context of aberrant glucose metabolism in GBM.

Results: The brown module was the key module for GBM, and 8 critical genes were obtained for ROC analysis. Peroxidasin (PXDN) was identified as the critical gene associated with glycolysis in GBM. In in vitro experiments, elevated PXDN expression in GBM cell lines was quantified through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. PXDN knockdown significantly reduced glycolytic flux and impeded the malignant phenotypes of GBM cells by downregulating Lactate Dehydrogenase A (LDHA) expression. In vivo experiments demonstrated that PXDN knockdown effectively suppressed GBM growth. Conversely, LDHA overexpression not only promoted these malignant phenotypes and glycolytic capacity but also substantially reversed the tumor-suppressive effects induced by PXDN knockdown.

Discussion: PXDN is identified as a potential diagnostic indicator for GBM, and PXDN promotes malignant progression in GBM by modulating LDHA. Anti-PXDN therapy may represent a viable new approach to combat GBM.

Glioblastoma; PXDN; Warburg effect; databases genetic; glycolysis.