N6-methyladenosine-modified circ_0000517 promotes non-small cell lung cancer metastasis via miR-1233-3p/CDH6 axis.

Circular RNAs (circRNAs) exhibit dysregulation in non-small cell lung cancer (NSCLC) and regulate the malignant biological behavior of NSCLC. The N6-methyladenosine (m6A) modification of circRNAs plays a critical role in multiple malignant tumors, and their biological relevance in NSCLC is unclear. Herein, this study was conducted to investigate the novel functional mechanism of highly expressed circ_0000517 in NSCLC by developing in vitro experiments. We found that circ_0000517 was upregulated in NSCLC tissues and cells, and that increased circ_0000517 expression was associated with m6A modification. Biologically, silenced circ_0000517 hindered the proliferation, colony formation, migration and invasion of NSCLC cells in vitro, and also suppressed the EMT-related process. Mechanistically, highly expressed circ_0000517 activated CDH6 expression and EMT evolution through sponging miR-1233-3p. Notably, miR-1233-3p had the opposite effect and reversed the promotion effect of circ_0000517 on the malignant biological behavior of NSCLC cells. Our study revealed a promising novel endogenous regulatory network that m6A-modified circ_0000517 accelerated malignant evolution of NSCLC by targeting the miR-1233-3p/CDH6 axis.