Cancer Management and Research (2020-12-01)

CircSKA3 Modulates FOXM1 to Facilitate Cell Proliferation, Migration, and Invasion While Confine Apoptosis in Medulloblastoma via miR-383-5p

  • Wang X,
  • Xu D,
  • Pei X,
  • Zhang Y,
  • Zhang Y,
  • Gu Y,
  • Li Y

Journal volume & issue
Vol. Volume 12
pp. 13415 – 13426

Abstract

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Xinfang Wang,* Dong Xu,* Xin Pei, Yingying Zhang, Yuling Zhang, Yaxing Gu, Ying Li Department of Pediatrics, Shandong Provincial Western Hospital, Jinan 250022, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying LiDepartment of Pediatrics, Shandong Provincial Western Hospital, No. 4 Duanxing West Road, Jinan, Shandong 250022, People’s Republic of ChinaTel +86-531 83086400Email [email protected]: 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

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