miR-451 suppresses EMT and metastasis in glioma cells

被引:31
作者
Nan, Yang [1 ,2 ,3 ]
Guo, Liyun [4 ]
Lu, Yalin [1 ]
Guo, Gaochao [5 ]
Hong, Rujun [1 ]
Zhao, Liwen [2 ]
Wang, Le [1 ,2 ]
Ren, Bingcheng [1 ,2 ]
Yu, Kai [1 ]
Zhong, Yue [1 ,2 ,3 ]
Huang, Qiang [1 ,2 ,3 ]
机构
[1] Tianjin Med Univ Gen Hosp, Dept Neurosurg, Tianjin 300052, Peoples R China
[2] Tianjin Med Univ Gen Hosp Airport Site, Dept Neurosurg, Tianjin, Peoples R China
[3] Tianjin Key Lab Injuries Variat & Regenerat Nervo, Tianjin, Peoples R China
[4] Tianjin Med Univ Gen Hosp Airport Site, Dept Hemodialysis Ctr, Tianjin, Peoples R China
[5] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Neurosurg, Peoples Hosp, Zhengzhou, Peoples R China
关键词
Glioma; miRNA-451; CAB39; EMT; Pi3k; Akt; Snail signaling pathway; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER-CELLS; INVASION; PROLIFERATION; PI3K/AKT; MIGRATION; GLIOBLASTOMA; ACTIVATION; PATHWAY;
D O I
10.1080/15384101.2021.1933303
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The metastasis of tumor cells is a challenge for the clinical treatment of glioma. Epithelial-mesenchymal transition (EMT) contributes to glioma cell invasiveness. Our previous study confirmed that the expression of miRNA-451, which inhibits the PI3K/Akt signaling pathway by directly targeting CAB39 and plays a repressive role in glioma, is downregulated in glioma. However, the specific mechanism of miRNA-451 regulation in glioma is unclear. In this study, we investigated whether miRNA-451 blocks the processes of EMT and metastasis in glioma cells in vivo and in vitro. By targeting CAB39, miRNA-451 likely triggers the PI3K/Akt/Snail signaling pathway to reduce glioma proliferation, invasion, migration and EMT. We used Western blotting experiments to demonstrate that overexpression of miRNA-451 significantly reduced p-AKT(Ser473), N-cadherin, Vimentin, Twist, Snail and Cyclin D1 expression and increased E-cadherin expression. We demonstrated that overexpression of miR-451 suppressed glioma cell proliferation, invasion, migration and EMT by MTT and colony formation assays, Transwell assays, wound healing assays and animal experiments. Taken together, these results suggest that miRNA-451 can reduce EMT and metastasis in glioma cells through the suppression of the PI3K/Akt/Snail signaling pathway by targeting CAB39 in vitro and in vivo. miR-451 may be a new target for glioma treatment.
引用
收藏
页码:1270 / 1278
页数:9
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