IGF2BP2-mediated m6A modifies SLC7A11 to regulate proliferation and ferroptosis in non-small cell lung cancer cells

Background. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is implicated in various cancers, but its role in modulating ferroptosis and tumor cell behavior in non-small cell lung cancer (NSCLC) remains unclear. Objectives. This study aimed to investigate how IGF2BP2-mediated N6-methyladenosine (m6A) modification of solute carrier family 7 member 11 (SLC7A11) affects ferroptosis and NSCLC cell viability. Materials and methods. NSCLC H1299 cells were transfected with either IGF2BP2 or SLC7A11 plasmids and corresponding siRNAs. Expression levels of IGF2BP2, SLC7A11 and ferroptosis markers were analyzed using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) and lipid peroxidation levels were measured with flow cytometry and biochemical kits. The RNA immunoprecipitation (RIP) and mRNA stability assays were utilized to explore the interaction between IGF2BP2 and SLC7A11. Results. IGF2BP2 expression was significantly upregulated in H1299 cells. Overexpression of IGF2BP2 enhanced cell viability and decreased ferroptosis, whereas its knockdown resulted in reduced cell viability and increased ferroptotic activity. IGF2BP2 enhanced SLC7A11 mRNA stability through m6A modification, and SLC7A11 overexpression reversed the effects of IGF2BP2 knockdown. This interaction increased cell viability and reduced ROS and lipid peroxidation. Conclusions. IGF2BP2 plays a critical role in NSCLC by stabilizing SLC7A11 mRNA via m6A modification, promoting cell proliferation and suppressing ferroptosis. Targeting the IGF2BP2-SLC7A11 axis may offer a promising therapeutic strategy for NSCLC.