Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Suppresses Ferroptosis in Non-Small Cell Lung Cancer via Stabilizing m6A Modification of Fanconi Anemia Group D2 Protein

Abstract

This study investigated the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in non-small cell lung cancer (NSCLC) and its association with N6-methyladenosine (m6A) modification. The study analyzes the expression levels and stability of IGF2BP3, as well as its impact on NSCLC cell functions. The findings indicate that IGF2BP3 is upregulated in NSCLC patients and cell lines. Knocking down IGF2BP3 reduces cell proliferation and promotes ferroptosis in A549 and H1299 cells. Additionally, the study reveals that IGF2BP3 regulates the m6A modification of the fanconi anemia group D2 protein (FANCD2) and influences its mRNA stability. Overexpressing FANCD2 counteracts the effects of IGF2BP3 silencing and increases the aggressiveness of NSCLC. Furthermore, treatment with celastrol induces ferroptosis in NSCLC cells and inhibits tumor growthin vivo. In conclusion, these findings suggest that IGF2BP3 acts as an oncogene in NSCLC. Its interaction with FANCD2 through m6A modification suppresses ferroptosis in NSCLC cells. Thus, the IGF2BP3/FANCD2 signaling pathway may serve as a potential therapeutic target for NSCLC.