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ABSTRACT Circular RNAs (CircRNAs) are reported to exert vital regulatory roles in the occurrence and development of various human malignancies, including non-small cell lung cancer (NSCLC). Bioinformatics methods identified the… Click to show full abstract
ABSTRACT Circular RNAs (CircRNAs) are reported to exert vital regulatory roles in the occurrence and development of various human malignancies, including non-small cell lung cancer (NSCLC). Bioinformatics methods identified the down-regulation of circSCN8A (circBase ID: hsa_circ_0026337) in NSCLC tissues. However, its biological functions and molecular mechanisms in NSCLC remain unknown. In this study, we found that circSCN8A expression was down-regulated in NSCLC tissues and cells. Low circSCN8A expression was positively associated with aggressive clinicopathological characteristics and poor prognosis in NSCLC patients. CircSCN8A suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and blocked tumor growth in vivo. Moreover, circSCN8A promoted cell ferroptosis in NSCLC. Mechanistically, circSCN8A acted as a competing endogenous RNA (ceRNA) by sponging miR-1290 to enhance the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Furthermore, the knockdown of ACSL4 or overexpression of miR-1290 reversed the effect of circSCN8A on facilitating ferroptosis and inhibiting cell proliferation and metastasis. In summary, circSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis. Thus, circSCN8A may represent a promising therapeutic target against NSCLC.