Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression via the miR-411-5p/RAB9A Axis

作者：Yining Xu, Yao Teng, Haonan Ni, Rujie Zheng, Kangmao Huang, Yizhen Huang, Jun Gao, Di Qiao, Shuying Shen, Jianjun Ma · 发表于：Research Square · 年份：2020 · DOI：10.21203/rs.3.rs-125943/v1 · 研究领域：Circular RNAs in diseases、RNA Interference and Gene Delivery、RNA Research and Splicing

Abstract BackgroundRecently, various studies have identified circular RNAs (circRNAs) to play a significant role in tumorigenesis, thereby showing potential as novel tumor biomarkers. circSIPA1L1 is a new-found circular RNA formed by back-splicing of SIPA1L1 and is found increased in osteosarcoma (OS). Nevertheless, the specific functions of circSIPA1L1 in OS remain unknown. MethodsIn the present study, circSIPA1L1 was obtained from a previously reported circRNA microarray (GSE96964) in the GEO database. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA level of circSIPA1L1 in OS cell lines and tissue samples. Bioinformatics analysis, luciferase reporter assays, real-time PCR, RNA pull-down assays and RNA immunoprecipitation (RIP) were employed to verify the binding of circSIPA1L1 with miR-411-5p. Xenograft tumor models were established to identify the role of circSIPA1L1 in vivo . A series of in-vitro experiments, such as western blotting , colony formation, transwell assays and anoikis assay were employed to confirm the relationship across circSIPA1L1, miR-411-5p, and RAB9A. ResultsOur study confirmed circSIPA1L1 to be upregulated in both human OS samples and OS cell lines. Mechanistically, circSIPA1L1 could serve as a miR-411-5p molecular sponge to increase RAB9A expression, which was confirmed to be a tumor promoter mediating carcinogenesis. Silencing of circSIPA1L1 attenuated the vitality, invasion, migration and proliferation of ...