CircRNA LNPEP has been shown to promote the development of hepatocellular carcinoma, but its function in ovarian cancer (OC) remains unclear. The Kaplan-Meier method was used to analyze the clinical significance of circLNPEP expression in OC patients. The stability of circLNPEP was detected by actinomycin D and RNase R treatment. The correlations between miR-876-3p and two genes (circLNPEP and WNT5A) were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assay. Expressions of circLNPEP, miR-876-3p, and WNT5A were determined by qRT-PCR and western blot. The effect of circLNPEP/miR-876-3p/WNT5A axis on viability, proliferation, migration, and invasion, and angiogenesis of cells was determined by cell function experiment and rescue experiment. Xenograft tumor mice were constructed for in vivo verification. Expressions of apoptosis, epithelial mesenchymal transition (EMT)-related genes, and CD34 were determined by qRT-PCR, western blot and immunohistochemistry. High level of circLNPEP was related to poor prognosis in OC. CircLNPEP was highly expressed in OC tissues and cell lines, mainly distributed in the cytoplasm, while miR-876-3p was the opposite. MiR-876-3p targeted and negatively correlated with circLNPEP and WNT5A. Sh-circLNPEP repressed cell viability, proliferation, migration, invasion, angiogenesis, and EMT but promoted apoptosis, which were related to its regulation of expression of EMT- and apoptosis-related genes, WNT5A, and CD34. The regulatory effect of sh-circLNPEP can be reversed by miR-876-3p inhibitor, and that of miR-876-3p inhibitor can be reversed by sh-WNT5A. CircLNPEP promoted cancer cell proliferation, EMT and angiogenesis, and inhibited apoptosis by regulating miR-876-3p/WNT5A axis.
Keywords: Circlnpep; WNT5A; epithelial mesenchymal transition; miR-876-3p; ovarian cancer.