Circ_0001068 accelerates the development of ovarian cancer by promoting FXYD5 expression through inhibiting mir-149-5p activity

Abstract

Abstract Background Ovarian cancer (OC) is one of the common malignancies of the female reproductive organs. Microarray analysis shows that circ_0001068 is upregulated in OC patients, however, its carcinogenic effect on OC development has not yet been revealed. Methods In this study, qRT-PCR and western blotting were used to determine the expression of circ_0001068, microRNA-149-5p (miR-149-5p) and domain containing ion transport regulator 5 (FXYD5). Clone formation was used to assess cell proliferation, and transwell assays were performed to analyze cell migration and invasion. Dual-luciferase reporter and pull down assays were used to verify the binding relationship between circ_0001068 and miR-149-5p or FXYD5. Mouse xenograft tumor formation was performed to validate the role of circ_0001068 in vivo. Results We found that the expression levels of circ_0001068 and FXYD5 were significantly increased in OC tissues and cell lines. Circ_0001068 knockdown significantly inhibited cell proliferation, migration, invasion, glycolysis, and glutamine metabolism. Circ_0001068 directly interacted with miR-149-5p, and the introduction of miR-149-5p mimics in OC cells partially reversed circ_0001068 knockdown-mediated effects. MiR-149-5p directly interacted with the 3’untranslated region (3’UTR) of FXYD5, and FXYD5 overexpression partially counteracted circ_0001068 knockdown-mediated effects in OC cells. Circ_0001068 knockdown inhibited xenograft tumor growth in vivo. Conclusion Our findings suggest that circ_0001068 promotes the malignant properties of OC cells by targeting the miR-149-5p/FXYD5 axis.

Keywords

• Ovarian cancer
• Circ_0001068
• MiR-149-5p
• FXYD5