Abstract
Gastric cancer (GC) has become the fifth largest malignant tumor in the world, with a mortality rate ranking fourth. IGF2BP3, as a multifunctional RNA binding protein, is involved in regulating alternative splicing (AS) and m6A modification, and plays a carcinogenic role in the development of gastric cancer, while little is known about the impact of IGF2BP3 on alternative splicing in gastric cancer cells and the underlying mechanism. In this study, we overexpressed IGF2BP3 (IGF2BP3-OE) in gastric cancer AGS cells and obtained transcriptome sequencing data (RNA-seq) to explore the effects of IGF2BP3 on gene expression and AS. The RNA binding profile of IGF2BP3 was utilized to identify how IGF2BP3 binds to and modulate expression and AS patterns of target genes. IGF2BP3-OE resulted in 479 differentially expressed genes (DEGs), majority of which were downregulated. We selected 20 DEGs and validated their expression pattern by RT-qPCR experiment, including ZFAS1, DUSP9, GPX3, IDH2, and H19 that were associated with GC development. More importantly, IGF2BP3-OE significantly modulated AS pattern of thousands of genes, which were enriched in mRNA splicing, cell proliferation, and translation pathways. By integrating the RNA binding profile of IGF2BP3, we found IGF2BP3 binding preferred to modulate the splicing pattern of bound genes, and the overlapped genes were also enriched in mRNA splicing pathways. We validated the AS pattern changes of S100A4 and PLK3 by RT-qPCR. IGF2BP3 probably modulate GC development by regulating AS profile in GC cells. In summary, we explored the dysregulated transcriptome profile that IGF2BP3 affects gene expression and alternative splicing by binding to mRNA, and thus plays a role in the development of GC cells. The IGF2BP3 and identified targets has potential value for GC treatment in future.