MiR-92b inhibitor promoted glioma cell apoptosis via targeting DKK3 and blocking the Wnt/beta-catenin signaling pathway

被引:47
|
作者
Li, Qifeng [1 ]
Shen, Ke [2 ,3 ]
Zhao, Yang [1 ]
Ma, Chenkai [1 ]
Liu, Jianwen [2 ,3 ]
Ma, Jie [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Pediat Neurosurg, Shanghai 200092, Peoples R China
[2] E China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China
[3] E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China
来源
基金
中国国家自然科学基金;
关键词
miR-92b; DKK3; The Wnt/beta-catenin signaling pathway; Glioma; Prognosis; MICRORNAS; CANCER; EXPRESSION; GENES;
D O I
10.1186/1479-5876-11-302
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: MiR-92b was upregulated in gliomas. However, the association of miR-92b with glioma cell apoptosis and survival remains unknown. Methods: Proliferation capability of glioma cells upon tranfection with miR-92b mimics or inhibitors was detected by mutiple analyses, including MTT assays, colony formation assay. Apoptosis abilities of glioma cells were detected by flow cytometric analysis. The target of miR-92b was determined by luciferase reporter and western blot. The association of miR-92b with outcome was examined in twenty glioma patients. Results: MiR-92b expression was significantly increased in high-grade gliomas compared with low-grade gliomas, and positively correlated with the degree of glioma infiltration. Over-expression of miR-92b increased cell proliferation, whereas knockdown of miR-92b decreased cell proliferation via modulating the levels of the target, Target prediction analysis and a dual luciferase reporting assay confirmed that the inhibitory protein-coding Dickkopf-3 gene (DKK3) was a direct target of miR-92b. Furthermore, miR-92b could regulate the expression of downstream genes of the Wnt/beta-catenin signaling pathway, such as Bcl2, c-myc and p-c-Jun, in glioma cells. Finally, the increased level of miR-92b expression in high-grade gliomas confers poorer overall survival. Conclusions: The present data indicates that miR-92b directly regulate cell proliferation and apoptosis by targeting DKK3 and act as prognostic factors for glioma patients.
引用
收藏
页数:9
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