Cargando…
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: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
|
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 |
_version_ | 1783670368013123584 |
---|---|
author | Wang, Zheng Wang, Xiaoxi Cheng, Fei Wen, Xue Feng, Shi Yu, Fang Tang, Hui Liu, Zhengjin Teng, Xiaodong |
author_facet | Wang, Zheng Wang, Xiaoxi Cheng, Fei Wen, Xue Feng, Shi Yu, Fang Tang, Hui Liu, Zhengjin Teng, Xiaodong |
author_sort | Wang, Zheng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7997605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-79976052021-03-30 Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis Wang, Zheng Wang, Xiaoxi Cheng, Fei Wen, Xue Feng, Shi Yu, Fang Tang, Hui Liu, Zhengjin Teng, Xiaodong Cancer Manag Res Original Research 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. Dove 2021-03-22 /pmc/articles/PMC7997605/ /pubmed/33790644 http://dx.doi.org/10.2147/CMAR.S298468 Text en © 2021 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Zheng Wang, Xiaoxi Cheng, Fei Wen, Xue Feng, Shi Yu, Fang Tang, Hui Liu, Zhengjin Teng, Xiaodong Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis |
title | Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis |
title_full | Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis |
title_fullStr | Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis |
title_full_unstemmed | Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis |
title_short | Rapamycin Inhibits Glioma Cells Growth and Promotes Autophagy by miR-26a-5p/DAPK1 Axis |
title_sort | rapamycin inhibits glioma cells growth and promotes autophagy by mir-26a-5p/dapk1 axis |
topic | Original Research |
url | 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 |
work_keys_str_mv | AT wangzheng rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT wangxiaoxi rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT chengfei rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT wenxue rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT fengshi rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT yufang rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT tanghui rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT liuzhengjin rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis AT tengxiaodong rapamycininhibitsgliomacellsgrowthandpromotesautophagybymir26a5pdapk1axis |