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28 August 2019 : Laboratory Research  

Circular RNA CircMTO1 Inhibits Proliferation of Glioblastoma Cells via miR-92/WWOX Signaling Pathway

Xuewen ZhangBCDEF, Bo ZhongBCDEF, Wenjie ZhangCF, Jie WuAG

DOI: 10.12659/MSM.918676

Med Sci Monit 2019; 25:6454-6461


BACKGROUND: Circular RNA circMTO1 has been reported to inhibit the progression of many types of cancers. However, the role of circMTO1 in the progression of glioblastoma remains unclear. The purpose of our study was to explore the potential involvement of circMTO1 in glioblastoma.

MATERIAL AND METHODS: The expression of circMTO1 in human glioblastoma tissues was determined via quantitative real-time polymerase chain reaction (qRT-PCR). The effect of circMTO1 on proliferation of human glioblastoma cell line U251 was assessed through the Cell Counting Kit-8 (CCK-8) and colony formation assay. The regulatory interaction between circMTO1 and miR-92 was explored by bioinformatics prediction and luciferase reporter assay.

RESULTS: We showed that circMTO1 was markedly downregulated in glioblastoma tissues compared with adjacent normal tissues. Lower circMTO1 level was significantly associated with shorter overall survival among patients with glioblastoma. In addition, circMTO1 inhibited proliferation of cell U251 cells. Mechanistically, circMTO1 upregulates the expression of WWOX in U251 cells, and WWOX mediates circMTO1-induced inhibition of proliferation of U251 cells. In addition, miR-92 downregulates the expression of WWOX by the targeting its mRNA 3’ UTR. More importantly, circMTO1 directly interact with miR-92, and subsequently serves as a miRNA sponge to upregulate WWOX expression.

CONCLUSIONS: Our results demonstrate that circMTO1 inhibits the proliferation of glioblastoma cells via the miR-92/WWOX signaling pathway.

Keywords: Cell Proliferation, Glioblastoma, MicroRNAs, Base Sequence, Brain Neoplasms, Gene Expression Regulation, Neoplastic, Prognosis, RNA, Circular, Signal Transduction, Tumor Suppressor Proteins, WW Domain-Containing Oxidoreductase


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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416