Circ_SIPA1L1 Promotes Osteosarcoma Progression Via miR-379-5p/MAP3K9 Axis

Background: Osteosarcoma (OS) is a common malignant bone tumor. Circular RNAs (circRNAs) exert important roles in the pathogenesis of human cancers, including OS. In this study, the authors focused on the role and mechanism of circRNA signal-induced proliferation-associated 1 like 1 (circ_SIPA1L1) in OS. Methods: The enrichment of SIPA1L1, circ_SIPA1L1, microRNA-379-5p (miR-379-5p), and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The colony formation capacity was assessed through colony formation assay. Transwell assays were used to detect the migration and invasion abilities. Western blot assay was used to measure the expression of metastasis-related proteins and MAP3K9. The target interactions between the genes in circ_SIPA1L1/miR-379-5p/MAP3K9 axis were predicted by StarBase and confirmed by dual-luciferase reporter assay. The in vivo role of circ_SIPA1L1 was verified by murine xenograft assay. Results: Circ_SIPA1L1 abundance was aberrantly elevated in OS tissues and cell lines. Circ_SIPA1L1 accelerated the proliferation and metastasis abilities of OS cells. Circ_SIPA1L1 promoted the malignant behaviors of OS cells through elevating MAP3K9 level. MiR-379-5p directly bound to circ_SIPA1L1 and MAP3K9. MiR-379-5p interference rescued the abilities of proliferation and metastasis in OS cells, which were suppressed by the silencing of circ_SIPA1L1. Circ_SIPA1L1 promoted the development of OS via miR-379-5p/MAP3K9 in vivo. Conclusion: Circ_SIPA1L1 promoted the progression of OS via miR-379-5p/MAP3K9 axis.