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Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis
BACKGROUND: Glioma is a common intracranial malignant tumor with high rates of invasiveness and mortality. This study aimed to investigate the mechanism of rapamycin in glioma. METHODS: U118-MG cells were treated with and without rapamycin in vivo and then collected for RNA sequencing. Differentiall...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997605/ https://www.ncbi.nlm.nih.gov/pubmed/33790644 http://dx.doi.org/10.2147/CMAR.S298468 |
Sumario: | BACKGROUND: Glioma is a common intracranial malignant tumor with high rates of invasiveness and mortality. This study aimed to investigate the mechanism of rapamycin in glioma. METHODS: U118-MG cells were treated with and without rapamycin in vivo and then collected for RNA sequencing. Differentially expressed miRNAs (DEMs) were screened and verified. MiR-26a-5p was selected for functional verification, and the target gene of miR-26a-5p was identified. The effects of miR-26a-5p on cell proliferation, cell cycle, apoptosis, and autophagy were also investigated. RESULTS: In total, 58 up-regulated and 41 down-regulated DEMs were identified between rapamycin-treated and untreated U118-MG cells. MiR-26-5p levels were up-regulated in U118-MG cells treated with 12.5 μM rapamycin, and death-associated protein kinase 1 (DAPK1) expression, a direct miR-26a-5p target gene, was down-regulated. Rapamycin substantially inhibited cell proliferation and cell percentage in the S phase and promoted cell apoptosis; miR-26a-5p inhibitor increased cell proliferation and cell cycle and decreased cell apoptosis; DAPK1 overexpression further induced cell proliferation, increased the cell number in the S phase, and inhibited apoptosis in glioma cells. Notably, rapamycin increased the autophagy-related Beclin1 protein expression levels and the LC3 II/I ratio. CONCLUSION: Rapamycin exerts anti-tumor effects by promoting autophagy in glioma cells, which was dependent on the miR-26a-5p/DAPK1 pathway activation by rapamycin. |
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