Background: Non-small cell lung cancer (NSCLC) remains the most commonly diagnosed malignancy and the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have been demonstrated to play critical roles in human carcinogenesis, including NSCLC. However, it is still unclear whether circRNA nuclear factor I X (circNFIX) is implicated in the molecular pathogenesis of NSCLC.
Methods: The expression levels of circNFIX, miR-212-3p and a disintegrin and metalloproteinases 10 (ADAM10) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell viability was gauged by the Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were determined by transwell assays. Glucose uptake and lactate product were determined using the assay kits. Targeted relationships among circNFIX, miR-212-3p and ADAM10  were verified by dual-luciferase reporter and RNA pulldown assays. Additionally, the xenograft model assays were carried out to analyze the role of circNFIX in tumor growth in vivo.
Results: Our data revealed that circNFIX was overexpressed in NSCLC and predicted poor prognosis of NSCLC patients. CircNFIX knockdown suppressed NSCLC cell viability, migration, invasion and glycolysis in vitro and hampered tumor growth in vivo. Mechanistically, CircNFIX acted as a molecular sponge of miR-212-3p, and the repressive effect of circNFIX knockdown on NSCLC cell malignant progression was mediated by miR-212-3p. Moreover, ADAM10  was a direct target of miR-212-3p, and circNFIX influenced ADAM10  expression by sponging miR-212-3p in NSCLC cells. Furthermore, the silencing of ADAM10  hindered NSCLC cell viability, migration, invasion and glycolysis in vitro.
Conclusion: Our findings first identified that the knockdown of circNFIX, a highly expressed circRNA in NSCLC, exerted a repressive role in NSCLC malignant progression at least in part through targeting the miR-212-3p/ADAM10  axis, illuminating a novel understanding of circRNA regulation in NSCLC.
Keywords: NSCLC, circNFIX, miR-212-3p, ADAM10, malignant progression