Circular RNAs (circRNAs) play critical roles in the recurrence and progression of non-small-cell lung cancer (NSCLC). This study aimed to investigate the function and underlying mechanism of a novel circRNA (circRPPH1) in NSCLC. Localization of circRPPH1 was determined via FISH assay, while cell proliferation was assessed via CCK8 and colony formation assay. Cell migration and invasion were studied using transwell assay, while binding sites between miR-326 and circRPPH1 or ERBB4 were verified by luciferase reporter, RIP, and RNA pull-down assays. Moreover, xenograft assay was performed to verify the in vivo roles of circRPPH1. Results indicated that circRPPH1 was highly expressed in NSCLC tissues and cells, where circRPPH1 levels were predictive of poor prognosis. The malignant behavior of NSCLC cells was exacerbated by overexpressing circRPPH1, while opposite effects were observed when it was knocked down. Direct interaction between miR-326 and circRPPH1 or ERBB4 was confirmed in NSCLC cells, while rescue experiment results showed that circRPPH1 exerted an oncogenic role via miR-326-ERBB4 signal axis. Moreover, in vitro, growth of NSCLC cells was significantly attenuated following circRPPH1 depletion. The study concluded that circRPPH1 was involved in promoting NSCLC progression via the miR-326/ERBB4 axis, which provided a novel potential target for the diagnosis or treatment of NSCLC.
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