IGF2BP3 Promotes Lung Cancer Progression Through FTO Dependent m6A Modification by Stabilizing N-myc

Background: N6-methyladenosine modification has been involved in various biological processes. However, its role in non-small cell lung cancer has not been well studied. Here, we show that IGF2BP3, as an transcription factor, plays a critical oncogenic role in non-small-cell lung cancer carcinogenesis through activating FTO expression and inducing aberrant m6A modification. Methods: : To evaluate the role of IGF2BP3 in non-small-cell lung cancer, we performed cell proliferation and cell cycle assays in three lung cancer cell lines. Lung cancer mouse model is used to examine the effects of IGF2BP3/FTO/N-myc on lung proliferation potentials in vivo. We analyzed the correlation between IGF2BP3 and FTO, IGF2BP3 and N-myc protein in colon cancer patients by Pearson correlation. To finally explore the relationship of IGF2BP3/FTO/N-myc, we used western blots, proliferation and cell cycle assays to confirm that IGF2BP3 may regulate lung cancer progression through FTO dependent m6A modification by stabilizing N-myc. Results: : We first identified that IGF2BP3 overexpressed in non-small-cell lung cancer tissue and cells. Then, we showed that FTO was the dysregulated factor responsible for the abnormal N6-methyladenosine modification in non-small-cell lung cancer. The loss-of-function assay demonstrated that IGF2BP3 enhances FTO-mediated cell proliferation and promotes cell apoptosis, through regulating expression of target gene N-myc by reducing m6A level in mRNA transcript. Conclusion: Our study demonstrates the functional importance of IGF2BP3 and N6-methyladenosine methylation modification in the tumor progression of non-small-cell lung cancer, and provides profound insights into lung carcinogenesis and drug response.