Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression Through the miR-411-5p/RAB9A Signaling Pathway.

Recently, various studies have identified circular RNAs (circRNAs) to play a significant role in tumorigenesis, thereby showing potential as novel tumor biomarkers. circSIPA1L1 is a newly discoveredcircular RNA, which is formed by back-splicing of SIPA1L1 and is found increased in osteosarcoma (OS). Nevertheless, the specific functions of circSIPA1L1 in OS remain unknown. In the present study, circSIPA1L1 was obtained from a previously reported circRNA microarray in the GEO database (GSE96964). 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. Our 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 OS cell lines both in vivo and in vitro. miR-411-5p inhibition or RAB9A overexpression reversed the anti-tumor effects caused by circSIPA1L1 knockdown. Briefly, circSIPA1L1 could function as a driver gene in OS and initiate OS tumorigenesis through the miR-411-5p/RAB9A signaling pathway, which might become a potential therapeutic biomarker for OS treatment. Copyright © 2021 Xu, Yao, Ni, Zheng, Huang, Huang, Gao, Qiao, Shen and Ma.

Citation

Yining Xu, Teng Yao, Haonan Ni, Rujie Zheng, Kangmao Huang, Yizhen Huang, Jun Gao, Di Qiao, Shuying Shen, Jianjun Ma. Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression Through the miR-411-5p/RAB9A Signaling Pathway. Frontiers in cell and developmental biology. 2021;9:642605

PMID: 33968929

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