hsa_circ_0005963 downregulation suppresses NSCLC malignant progression by miR-506-3p/SOX9-mediated stemness regulation

PURPOSE: This study investigated the role and regulatory mechanisms underlying hsa_circ_0005963 in NSCLC. METHODS: FISH and RT-qPCR were used to assess hsa_circ_0005963 expression in NSCLC cells and tissues. Dual-luciferase reporter assay was employed to characterize hsa_circ_0005963 downstream targets. Transwell migration and EdU incorporation were performed to detect NSCLC cell proliferation and migration. A mouse tumor xenograft model was constructed to assess hsa_circ_0005963 functions in NSCLC metastasis and progressions. RESULTS: hsa_circ_0005963 expression was upregulated in NSCLC tissues and cells. High hsa_circ_0005963 expression indicates poor prognosis, including overall survival. hsa_circ_0005963 silencing inhibited NSCLC proliferation and migration. Experiments confirmed that hsa_circ_0005963 downregulation suppresses A549 tumor invasions. A dual-luciferase reporter assay identified SOX9 and microRNA as hsa_circ_0005963 downstream targets, which was validated by RT-qPCR. SOX9 overexpression or miR-506-3p downregulation reversed the hsa_circ_0005963 silencing inhibitory effects upon proliferation and migrations. SOX9 overexpression reversed miR-506-3p effects to inhibit proliferation and migration in both cell lines. CONCLUSION: hsa_circ_0005963 promotes NSCLC development by sponging miR-506-3p to enhance SOX9 expression.