Abstract
BACKGROUND: Emerging evidence has shown that circular RNAs (circRNAs) are vital regulators in osteosarcoma (OS) progression. However, the effects of circ_WWC3 in OS have not been explored. In this research, the functions and mechanisms of circ_WWC3 in OS were investigated. METHODS: Quantitative reverse trancription polymerase chain reaction (qRT-PCR) was adopted to determine the levels of circ_WWC3, WW and WWC3 mRNA, miR-421, and phosphodiesterase 7B (PDE7B) mRNA. RNase R assay was used to determine the characteristic of circ_WWC3. Colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay were applied for cell growth. Transwell assay was performed for cell migration and invasion. Flow cytometry analysis was utilized for cell apoptosis. Western blot assay was conducted for the levels of apoptosis-related proteins and PDE7B protein. Dual-luciferase reporter assay was carried out to analyze the targeting relationship between miR-421 and circ_WWC3 or PDE7B. The murine xenograft model was established to explore the effect of circ_WWC3 in vivo. RESULTS: Compared to normal tissues and cells, circ_WWC3 and PDE7B were downregulated in OS tissues and cells. Overexpression of circ_WWC3 or PDE7B suppressed OS cell growth, migration, and invasion and promoted apoptosis in vitro. Regarding the mechanism analysis, circ_WWC3 positively modulated PDE7B expression by targeting miR-421. MiR-421 overexpression restored the impacts of circ_WWC3 on OS cell growth, metastasis, and apoptosis. Inhibition of miR-421 repressed the malignant behaviors of OS cells by targeting PDE7B. In addition, circ_WWC3 inhibited the tumorigenicity of OS in vivo. CONCLUSION: Circ_WWC3 overexpression slowed the development of OS by elevating PDE7B via sponging miR-421.