Circular RNA circDOCK1 contributes to osteosarcoma progression by acting as a ceRNA for miR-936 to regulate LEF1

Abstract

Background: Osteosarcoma (OS) is a serious bone malignancy that commonly occurred in humans. Recent research suggested that circular RNA (circRNA) Dedicator of cytokinesis 1 (circDOCK1, also called hsa_circ_0020378) enrolled in the tumorigenesis of osteogenic sarcoma. This subject aimed to explore the precise role and mechanism of circDOCK1 on OS progression. Methods: CircDOCK1, microRNA-936 (miR-936), and Lymphoid enhancer binding factor 1 (LEF1) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), colony formation, 5-ethynyl-2′-deoxyuridine (EdU), transwell, wound healing, and tube formation assays were used to assess OS cell proliferation, migration, invasion, and angiogenesis. Western blot analysis of protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP2), MMP9, and LEF1. According to bioinformatics software (circular RNA Interactome and TargetScan) analysis, the binding between miR-936 and circDOCK1 or LEF1 was predicted, followed by verification by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Results: Increased circDOCK1 and LEF1, and decreased miR-936 were found in OS tissues and cell lines. Furthermore, circDOCK1 silencing might suppress OS cell proliferation, migration, invasion, and angiogenesis in vitro. Bioinformatics analysis exhibited that circDOCK1 acted as a sponge for miR-936 and LEF1 was a downstream target of miR-936. Moreover, circDOCK1 functions through modulation of the miR-936/LEF1 axis. Conclusion: CircDOCK1 knockdown might attenuate OS cell malignant biological behaviors by regulating the miR-936/GFRA1 axis, which may highlight the diagnostic and therapeutic potential of these molecules for OS treatment.

Keywords

• CircDOCK1
• miR-936
• LEF1
• Osteosarcoma
• Proliferation