CircRNA PRH1-PRR4 stimulates RAB3D to regulate the malignant progression of NSCLC by sponging miR-877-5p

Background: Previous reports have confirmed the importance of circular RNA (circRNA) in the malignant progression of non-small-cell lung cancer (NSCLC). However, the role of circRNA PRH1-PRR4 readthrough (circPRH1-PRR4) in NSCLC progression was unclear. This study was designed to reveal the mechanism behind circPRH1-PRR4 regulating NSCLC progression.

Methods: Quantitative real-time polymerase chain reaction and western blot were employed to detect the expression of circPRH1-PRR4, microRNA-877-5p (miR-877-5p), the member RAS oncogene family (RAB3D), and other indicated protein markers. The positive expression rate of RAB3D was detected by immunohistochemistry assay. Cell proliferation was investigated by cell colony formation and 5-ethynyl-2'-deoxyuridine assays. Flow cytometry was employed to quantify apoptotic cells. Wound-healing and transwell invasion assays were used to evaluate cell metastasis. The interaction among circPRH1-PRR4, miR-877-5p, and RAB3D was identified by dual-luciferase reporter assay. In vivo assay was implemented to demonstrate the effect of circPRH1-PRR4 on tumor formation.

Results: As compared with controls, NSCLC tissues and cells displayed high expression of circPRH1-PRR4 and RAB3D, and low expression of miR-877-5p. Reduced expression of circPRH1-PRR4 resulted in inhibition of cell proliferation, migration, and invasion, but promotion of cell apoptosis in vitro. In support, circPRH1-PRR4 silencing inhibited tumor formation in vivo. Knockdown of miR-877-5p, a target miRNA of circPRH1-PRR4, relieved circPRH1-PRR4 absence-mediated action. Additionally, RAB3D was identified as a target mRNA of miR-877-5p. Importantly, circPRH1-PRR4 regulated RAB3D expression by miR-877-5p.

Conclusion: CircPRH1-PRR4 knockdown impeded NSCLC cell malignancy by the miR-877-5p/RAB3D pathway, providing a possible circRNA-targeted therapy for NSCLC.