Annexin A2: regulating glioma's fate and a potential therapeutic target

High recurrence and mortality in glioma are linked to aggressive proliferation. Recent strategies focus on genetic interventions, with Annexin A2 (ANXA2) emerging as a promising target. We wanted to evaluate ANXA2's prognostic value and its role in tumor progression, aiming to establish it as a viable therapeutic target. Bioinformatics analysis of public databases (The Cancer Genome Atlas, Chinese Glioma Genome Atlas, Rembrandt) was performed to validate ANXA2's prognostic significance. Functional assays (on cell lines U87 and U251) and in vivo studies were conducted to examine the impact of ANXA2 on cell proliferation, invasion, apoptosis, cell cycle progression, and tumor volume. Additionally, the relationship between ANXA2 and the Mitogen-Activated Protein Kinase (MAPK) signaling pathway was explored by analyzing key proteins' expression levels and phosphorylation states. Elevated ANXA2 expression correlated with poorer survival rates in glioma, showing variable expression across different grades and subtypes. Silencing ANXA2 impaired glioma cell motility and proliferation, induced apoptosis, altered cell cycle distribution, and reduced tumor volumes in vivo, at least partially through the MAPK pathway. This way, our study validates ANXA2 as a significant prognostic marker for glioma, contributing to tumor progression through the MAPK pathway, underscoring its potential as a therapeutic target.