Loss of ELAVL2 is associated with aggressive mesenchymal transition in glioblastoma

Abstract

Abstract Glioblastoma (GBM), the most lethal type of primary brain cancer, is characterized by cellular and molecular plasticity, which leads to intratumoral heterogeneity and hinders effective treatment. However, the regulation of such plasticity, including mesenchymal (MES) transition, is poorly understood. Here, we demonstrate that the RNA-binding protein ELAVL2 regulates aggressive MES transformation in GBM. ELAVL2 was most frequently deleted in GBM compared to other cancers and associated with distinct clinical and molecular features. ELAVL2-mediated transcriptomic alterations were indicative of GBM subtype signatures. Expression of ELAVL2 negatively correlated with that of epithelial-to-mesenchymal transition (EMT)-related genes, and its loss promoted the EMT process and chemo-resistance. Tissue microarray analysis revealed that high ELAVL2 protein expression level confers a favorable survival in GBM patients. On a molecular level, ELAVL2 regulated the expression of EMT-inhibitory molecules SH3GL3 and DNM3. Overall, these findings demonstrate ELAVL2 as a critical tumor suppressor that regulates MES transition in GBM, highlighting its role in transcriptomic plasticity and glioma progression.