Downregulation of miR‑186 promotes the proliferation and drug resistance of glioblastoma cells by targeting Twist1.

MOLECULAR MEDICINE REPORTS(2019)

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摘要
Temozolomide (TMZ) is widely used as a chemotherapeutic agent in the treatment of glioma; however, the development of drug resistance remains a major obstacle in the effective treatment of glioblastoma. Increasing evidence has indicated that microRNAs (miRs) are involved in the drug resistance of glioma; however, the role of miR-186-5p in the TMZ resistance of glioblastoma remains unknown. In the present study, the role of miR-186-5p in the resistance of glioblastoma to TMZ was investigated. mRNA and protein expression levels were detected via reverse transcription-quantitative PCR and western blot analysis, respectively. It was determined that miR-186-5p was significantly downregulated in glioblastoma tissues and cell lines. Additionally, the expression of miR-186-5p was decreased, whereas that of Twist1 was upregulated during the development of drug resistance in glioma cells. The introduction of miR-186 into glioblastoma cells via transfection decreased the proliferation and TMZ resistance of glioblastoma cells, as determined via 5-ethynyl-2 '-deoxyuridine and Cell Counting Kit-8 assays, whereas the inhibition of miR-186-5p induced opposing effects. Furthermore, luciferase reporter and expression rescue assays revealed that miR-186-5p bound to the 3 '-untranslated region of Twist-related protein 1 (Twist1). In conclusion, the present study demonstrated that downregulation of miR-186-5p may contribute to the proliferation and drug resistance of glioblastoma cells via the regulation of Twist1 expression. These results suggested that miR-186-5p may be a novel therapeutic target in the treatment of glioblastoma.
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关键词
microRNAs,microRNA-186,Twist,temozolomide,glioblastoma,glioma
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