Naringenin Inhibits Cell Migration, Invasion, and Tumor Growth by Regulating circFOXM1/miR-3619-5p/SPAG5 Axis in Lung Cancer

Background: Naringenin has been reported to play an anticancer role by inhibiting the metastasis of tumor cells, but the roles of naringenin and the molecular mechanisms mediated by it in lung cancer remain to be elucidated. Materials and Methods: Cell migration and invasion were determined by transwell assay. The expression levels of circular RNA FOXM1 (circFOXM1), microRNA-3619-5p (miR-3619-5p), and sperm-associated antigen 5 (SPAG5) in lung cancer were measured by quantitative real-time polymerase chain reaction. Western blot assay was used to detect the levels of all proteins. The interaction between microRNA and circular RNA or mRNA was validated using dual-luciferase reporter assay. The models of xenograft mice were established to evaluate the effect of naringenin on tumor growth in vivo. Results: Naringenin restrained migration and invasion of lung cancer cells in a dose-dependent manner. In addition, naringenin could decrease the expression levels of circFOXM1 and SPAG5, which were highly expressed in lung cancer and increase the level of miR-3619-5p with low expression in lung cancer in a dose-dependent manner. miR-3619-5p has an interactive relationship with circFOXM1 or SPAG5, and circFOXM1 could enhance SPAG5 expression by sponging miR-3619-5p in naringenin-treated lung cancer cells. Moreover, naringenin inhibited cell migration, invasion, and tumor growth by regulating circFOXM1/miR-3619-5p/SPAG5 axis in lung cancer. Conclusion: Naringenin hindered cell metastasis in vitro and tumor growth in vivo by reducing circFOXM1 and SPAG5 expression and inducing the expression of miR-3619-5p in lung cancer.

Keywords: SPAG5; circFOXM1; lung cancer; miR-3619-5p; naringenin.