METTL3-modified circRAD23B contributes to non-small cell lung cancer tumorigenesis and glycolysis via targeting miR-485-5p/ENO1 signaling

s Background Dysregulated circRNAs have been evidenced to be crucial drivers of non-small cell lung cancer (NSCLC). This study intended to characterize the biological properties of circRAD23B (circ_0001880) in NSCLC and its molecular mechanisms. Methods The abnormally upregulated circRNAs in NSCLC were identified from GSE146689 and detected via qRT-PCR. The biological characteristics of circRAD23B on NSCLC tumorigenesis and glycolysis were assessed in vitro and in vivo. m6A RNA immunoprecipitation was conducted to analyze the m6A modification of circRAD23B in NSCLC cells. Online bioinformatics analysis was conducted to predict downstream miRNA and mRNA (miR-485-5p/ ENO1 ) regulated by circRAD23B, and dual-luciferase reporter and rescue experiments were applied to verify whether circRAD23B drove NSCLC progression through targeting miR-485-5p/ ENO1 signaling. Results Highly expressed circRAD23B was validated in NSCLC, silencing of circRAD23B restrained the proliferation, metastasis, glycolysis of NSCLC cells. Moreover, METTL3 functioned as the m6A modifier of circRAD23B, and inhibition of METTL3 declined circRAD23B levels. Furthermore, the interplay between circRAD23B, miR-485-5p, and ENO1 was disclosed in NSCLC cells, circRAD23B sponged miR-485-5p ENO1 and enhanced ENO1 levels to facilitate NSCLC progression. Nevertheless, this study has several limitations, including a relatively small clinical sample size and the absence of validation using orthotopic xenograft and organoid models, which necessitates further experimental investigation. Conclusion The METTL3 /circRAD23B/miR-485-5p/ ENO1 axis may serve as a potential target for clinical NSCLC management.