IGF2BP2 orchestrates global expression and alternative splicing profiles associated with glioblastoma development in U251 cells

Abstract

Glioblastoma (GBM) is a highly invasive and malignant central nervous system tumor with a median survival duration of 15 months despite multimodal therapy. The insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) has been implicated in various cancers and is known to regulate RNA metabolism and alternative splicing (AS). However, its role in GBM remains unclear. Overexpression of IGF2BP2 led to significant alterations in gene expression, with 472 genes upregulated and 99 downregulated. Gene ontology (GO) analysis indicated enrichment in immune-related biological processes. Notably, IGF2BP2 was found to regulate AS events, with 1372 regulated AS genes (RASGs) and 2096 significantly distinct ASEs identified. Furthermore, IGF2BP2 selectively bound to 3′ and 5′ untranslated regions (UTRs) via GG[AU]C motifs, and IFIH1 was identified as a direct binding partner and upregulated gene upon IGF2BP2 overexpression. Functional enrichment analysis suggested that IGF2BP2 influences pathways related to RNA splicing and immune responses. Our findings demonstrate that IGF2BP2 plays a crucial role in GBM by modulating the transcriptome and AS events. The upregulation of immune-related genes and the regulation of AS by IGF2BP2 highlight its potential as a therapeutic target in GBM, particularly for immunotherapy. The study provides a foundation for further investigation into the molecular mechanisms of IGF2BP2 in GBM and its implications for cancer treatment.