Hsa_circ_0046263 Drives the Carcinogenesis and Metastasis of Non-Small Cell Lung Cancer Through the Promotion of NOVA2 by Absorbing Mir-940 as a Molecular Sponge

Background: Circular RNAs (circRNAs) have increasingly been investigated in different cancers due to their regulatory roles. In this study, hsa_circ_0046263 will be detailedly researched in non-small cell lung cancer (NSCLC).

Methods: The analyses of hsa_circ_0046263, microRNA-940 (miR-940), and neuro-oncological ventral antigen 2 (NOVA2) levels were administrated by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation detection was conducted using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell cycle and apoptosis were evaluated by flow cytometry. Transwell assay for migration and invasion was used to determine cell metastatic capacity. Overall protein levels were examined adopting Western blot. Target binding analysis was completed via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The effect of hsa_circ_0046263 on NSCLC in vivo was studied by xenograft model in mice.

Results: Hsa_circ_0046263 was overtly upregulated in NSCLC with important prognostic value. In vitro experiments indicated that hsa_circ_0046263 knockdown caused inhibitory effects on NSCLC cell proliferation, cell cycle, and metastasis but stimulative effect on apoptosis. Molecular mechanism analysis demonstrated that hsa_circ_0046263 served as a miR-940 sponge to act in the development of NSCLC. Moreover, miR-940 targeted NOVA2 and NOVA2 was regulated by hsa_circ_0046263/miR-940 axis. NOVA2 overexpression also neutralized the miR-940-mediated progression inhibition of NSCLC cells. In vivo assays suggested that hsa_circ_0046263 enhanced NSCLC tumorigenesis by targeting miR-940/NOVA2 axis.

Conclusion: Hsa_circ_0046263 was identified as a cancer-promoting factor in NSCLC via sponging miR-940 and upregulating NOVA2, which presented a clear mechanism of NSCLC occurrence and progression.