LTBP2 promotes meningioma progression by enhancing glycolysis via the PI3K/AKT/mTOR/c-Myc signaling pathway.

BACKGROUND: Meningiomas are common central nervous system tumors with few available treatment choices. This research investigates the role of LTBP2 in meningioma biology, emphasizing its ability to be a therapeutic goal. METHODS: Differentially expressed genes (DEGs) were recognized from the GSE84263 dataset. Weighted gene co-expression network analysis (WGCNA) revealed correlated gene modules. Hub genes were discovered via an analysis of the protein-protein interaction (PPI) network, with LTBP2 selected for further study. LTBP2 expression was analyzed utilizing Western blotting (WB) and quantitative reverse transcription-polymerase chain reaction in normal human meningeal cells (NHMCs) and meningioma cell lines. Functional assays assessed cell invasion and migration, proliferation, and apoptosis. Glycolysis was assessed through glucose uptake, lactate production, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) measurements. WB analysis assessed related protein levels in the PI3K/AKT and mTOR/c-Myc pathways in meningioma cells. RESULTS: The analysis identified 492 upregulated and 677 downregulated genes, with the green module significantly correlated. Six overlapping genes showed elevated expression in tumors. LTBP2 was upregulated in meningioma cells. Functional assays showed that LTBP2 knockdown reduced proliferation, invasion, and migration while increasing apoptosis, whereas its overexpression had the opposite effect, enhancing aggressive cellular behaviors. LTBP2 also promoted glycolysis, as shown by increased lactate production, glucose uptake and ECAR, along with decreasd OCR. Mechanistic studies revealed that LTBP2 activated the PI3K/AKT and mTOR/c-Myc signaling pathways, with c-Myc mediating the glycolytic effects of LTBP2. Importantly, c-Myc knockdown reversed the impacts of LTBP2 on cell invasion, proliferation, and apoptosis. CONCLUSION: LTBP2 plays a critical role in meningioma progression by activating the PI3K/AKT and mTOR/c-Myc signaling pathways, highlighting its potential as a biomarker and therapeutic target.