CircPVT1 promotes osteosarcoma glycolysis and metastasis by sponging miR-423-5p to activate Wnt5a/Ror2 signaling.

Abstract

Osteosarcoma (OS) is the most prevalent form of bone cancer. It has a high metastatic potential and progresses rapidly. The molecular mechanisms of OS remain unclear and this study aims to examine the functional role of circPVT1 and miR‐423‐5p in OS. Quantitative RT‐PCR (qRT‐PCR) and western blotting were used to examine levels of miR‐423‐5p, circPVT1, Wnt5a, Ror2, and glycolysis‐related proteins, including HK2, PKM2, GLUT1, and LDHA. Colony formation and transwell assays were used to test the roles of miR‐423‐5p, circPVT1, and Wnt5a/Ror2 in OS cell proliferation, migration, and invasion. Dual luciferase assay and Ago2‐RIP were used to validate the interactions of miR‐423‐5p/Wnt5a, miR‐423‐5p/Ror2, and circPVT1/miR‐423‐5p. Glucose uptake assay and measurement of lactate production were performed to assess the glycolysis process. A nude mouse xenograft model was used to evaluate the effects of sh‐circPVT1 and miR‐423‐5p mimics on tumor growth and metastasis in vivo. miR‐423‐5p was reduced in both OS tissues and OS cell lines, while Wnt5a/Ror2 and circPVT1 were elevated. miR‐423‐5p bound to 3′‐UTR of Wnt5a and Ror2 mRNA, and inhibited glycolysis and OS cell proliferation, migration, and invasion by targeting Wnt5a and Ror2. circPVT1 interacted with miR‐423‐5p and activated Wnt5a/Ror2 signaling by sponging miR‐423‐5p. Knockdown of circPVT1 or overexpression of miR‐423‐5p suppressed OS tumor growth and metastasis in vivo. miR‐423‐5p inhibited OS glycolysis, proliferation, migration, and metastasis by targeting and suppressing Wnt5a/Ror2 signaling pathway, while circPVT1 promoted those processes by acting as a sponge of miR‐423‐5p.