EIF4A3 induced CircCHD7 promote osteosarcoma progression by sponge miR-608 and regulated FZD4/MMP2 expression through Wnt/β-catenin pathway

Background: Osteosarcoma is a malignant tumor that tends to occur in adolescents. In recent years, surgical treatment has reduced mortality rates in patients with osteosarcoma. However, many patients still die of osteosarcoma, and further studies are needed to elucidate the complicated pathogenesis of this disease. Methods The function of circCHD7 was detected by transwell, clone formation, Cell Counting Kit 8, and apoptosis assays after knockdown of circCHD7 in 143B and HOS cells. Bioinformatics analysis was used to identify binding between miR-608 and circCHD7 , and the results were further validated using luciferase, pull-down, and RNA immunoprecipitation assays. Bioinformatics and quantitative real-time polymerase chain reaction were used to identify downstream target genes of miR-608 . The expression and effects of circCHD7 inhibitor were evaluated in stable sh- circCHD7 143B cell lines and a subcutaneous tumor model. Results CircCHD7 , regulated by eIF4A3, was found to promote tumor proliferation and migration. Knockdown of circCHD7 and overexpression of miR-608 enhanced apoptosis and inhibited migration ability in osteosarcoma cells. The inhibitory effects of circCDH7 knockdown in 143B and HOS cells could be rescued by miR-608 inhibitor. Bioinformatics and western blotting results showed that miR-608 could regulate the expression of downstream matrix metalloproteinase 2 (MMP2) and Frizzled-4 (FZD4) and further modulate the Wnt/β-catenin pathway, thereby exerting inhibitory effects on osteosarcoma. Conclusion In this study, we discovered a new circRNA, circCHD7 , that was regulated by eIF4A3 and modulated tumor growth through the miR-608 /FZD4/MMP2 pathway. These findings provide insights into the potential application of circRNAs in the treatment of osteosarcoma.