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miR-451 suppresses EMT and metastasis in glioma cells
Yang Nan1,2,3, Liyun Guo4, Yalin Lu1
1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Abstract:
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.
Insights
MicroRNA-451 (miRNA-451) suppresses glioma cell metastasis and epithelial-mesenchymal transition (EMT) by targeting CAB39 and inhibiting the PI3K/Akt/Snail pathway. This finding suggests miRNA-451 as a potential therapeutic target for glioma treatment.
Area of Science:
- Molecular Biology
- Oncology
- Neuroscience
Background:
- Glioma metastasis and epithelial-mesenchymal transition (EMT) pose significant challenges in clinical treatment.
- MicroRNA-451 (miRNA-451) is downregulated in glioma and known to inhibit the PI3K/Akt pathway by targeting CAB39.
- The precise regulatory mechanism of miRNA-451 in glioma progression remains largely undefined.
Purpose of the Study:
- To investigate the role of miRNA-451 in inhibiting EMT and metastasis in glioma cells.
- To elucidate the molecular mechanism by which miRNA-451 exerts its effects on glioma progression.
Main Methods:
- In vitro and in vivo experiments were conducted using glioma cell models.
- Overexpression of miRNA-451 was performed.
- Western blotting, MTT assays, colony formation assays, Transwell assays, wound healing assays, and animal experiments were utilized.
Main Results:
- Overexpression of miRNA-451 significantly reduced the expression of p-AKT(Ser473), N-cadherin, Vimentin, Twist, Snail, and Cyclin D1.
- E-cadherin expression was increased upon miRNA-451 overexpression.
- miRNA-451 suppressed glioma cell proliferation, invasion, migration, and EMT in vitro and in vivo.
Conclusions:
- MiRNA-451 inhibits EMT and metastasis in glioma cells by targeting CAB39 and suppressing the PI3K/Akt/Snail signaling pathway.
- MiRNA-451 demonstrates potential as a novel therapeutic target for glioma treatment.
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