Background: Dysregulation of circRNA expression is associated with increased metastasis and an adverse prognosis in non-small cell lung cancer (NSCLC). Herein, this study assessed the role and regulatory mechanism of circPVT1 in NSCLC development.
Methods: CircPVT1 expression was determined using qPCR. Functional assays, including cell proliferation, colony formation, and ferroptosis-related measurements (ROS, MDA, SOD, GSH and Fe2+ levels), were conducted following circPVT1 knockdown. The interactions between RNA and protein were determined through RIP, dual-luciferase reporter and fluorescence in situ hybridization. Actinomycin D assay was employed to test circPVT1 stability. Additionally, tumor progression in vivo was evaluated in xenograft models with U2AF65 knockdown.
Results: CircPVT1 was significantly elevated in NSCLC samples, correlating with worse clinical outcomes. Its knockdown resulted in diminished cell proliferation and increased ferroptosis. Mechanically, circPVT1 sponges miR-338-3p, facilitating GPX4 expression, which enhanced cell proliferation. U2AF65 bound to and stabilized circPVT1, promoting cell proliferation. In animal models, U2AF65 knockdown suppressed tumor progression by regulating the circPVT1/miR-338-3p/GPX4 signaling pathway.
Conclusions: U2AF65 stabilizes circPVT1 to promote NSCLC advancement through miR-338-3p suppression and GPX4 upregulation. Thus, circPVT1 and U2AF65 may be potential therapeutic targets in NSCLC.
Keywords: CircPVT1; Ferroptosis; GPX4; MiR-338-3p; NSCLC; U2AF65.
© 2025. The Author(s).