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CircSKA3 调节 FOXM1 以促进细胞增殖、迁移和侵袭,同时通过 miR-383-5p 限制髓母细胞瘤中的细胞凋亡
Authors Wang X, Xu D, Pei X, Zhang Y, Zhang Y, Gu Y, Li Y
Received 25 August 2020
Accepted for publication 2 December 2020
Published 30 December 2020 Volume 2020:12 Pages 13415—13426
DOI https://doi.org/10.2147/CMAR.S272753
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
Background: Medulloblastoma (MB) is the most common malignant brain tumor during childhood. Circular RNA (circSKA3) was identified to function as an oncogene in MB. However, the mechanism of circSKA3 in MB remains unclear.
Methods: The levels of circSKA3, microRNA-383-5p (miR-383-5p), and forkhead box M1 (FOXM1 ) in MB tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. The protein levels of B-cell lymphoma 2 (Bcl-2), C-Caspase3, and FOXM1 were detected via Western blot assay. Cell cycle was detected by flow cytometry. The migration and invasion abilities were monitored by Transwell assay. The dual-luciferase reporter assay was constructed to verify the interactions between miR-383-5p and circSKA3 or FOXM1 . The mice model experiment was carried out to validate the effects of circSKA3 in vivo.
Results: The levels of circSKA3 and FOXM1 were significantly elevated, while the level of miR-383-5p was notably declined in MB tissues. CircSKA3 was validated to sponge miR-383-5p, and FOXM1 was a candidate target of miR-383-5p. CircSKA3 silencing impeded cell proliferation, migration, and invasion while promoted apoptosis by targeting miR-383-5p in vitro and retarded xenograft tumor growth in vivo. miR-383-5p suppressed cell proliferation, migration, and invasion but promoted apoptosis in MB cells by regulating FOXM1. CircSKA3 depletion decreased FOXM1 expression via miR-383-5p in MB cells.
Conclusion: CircSKA3 augmented MB progression partly through miR-383-5p/FOXM1 axis.
Keywords: circSKA3, miR-383-5p, FOXM1 , medulloblastoma