Cargando…
MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1
Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here,...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772006/ https://www.ncbi.nlm.nih.gov/pubmed/29331678 http://dx.doi.org/10.1016/j.tranon.2017.12.008 |
_version_ | 1783293332232863744 |
---|---|
author | Li, Tengfei Ma, Ji Han, Xinwei Jia, Yongxu Yuan, Huifeng Shui, Shaofeng Guo, Dong |
author_facet | Li, Tengfei Ma, Ji Han, Xinwei Jia, Yongxu Yuan, Huifeng Shui, Shaofeng Guo, Dong |
author_sort | Li, Tengfei |
collection | PubMed |
description | Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively. The direct interaction between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of FoxM1, Sirt1 and γH2AX were measured by western blot assay. We found that miR-320 expression was down-regulated and FoxM1 expression was up-regulated in radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression dramatically enhanced radiosensitivity, promoted apoptosis, and improved γH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter assay and western blot assay further validated that miR-320 suppressed FoxM1 expression by directly targeting 3’ UTR region of FoxM1. Moreover, miR-320 inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore, overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase of radiosensitivity, apoptosis and γH2AX expression in glioma cells. In conclusion, miR-320 enhanced radiosensitivity of glioma cells through down-regulation of Sirt1 by directly targeting FoxM1. |
format | Online Article Text |
id | pubmed-5772006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57720062018-01-22 MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 Li, Tengfei Ma, Ji Han, Xinwei Jia, Yongxu Yuan, Huifeng Shui, Shaofeng Guo, Dong Transl Oncol Original article Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively. The direct interaction between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of FoxM1, Sirt1 and γH2AX were measured by western blot assay. We found that miR-320 expression was down-regulated and FoxM1 expression was up-regulated in radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression dramatically enhanced radiosensitivity, promoted apoptosis, and improved γH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter assay and western blot assay further validated that miR-320 suppressed FoxM1 expression by directly targeting 3’ UTR region of FoxM1. Moreover, miR-320 inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore, overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase of radiosensitivity, apoptosis and γH2AX expression in glioma cells. In conclusion, miR-320 enhanced radiosensitivity of glioma cells through down-regulation of Sirt1 by directly targeting FoxM1. Neoplasia Press 2018-01-11 /pmc/articles/PMC5772006/ /pubmed/29331678 http://dx.doi.org/10.1016/j.tranon.2017.12.008 Text en © 2017 Oncoinvent AS http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Li, Tengfei Ma, Ji Han, Xinwei Jia, Yongxu Yuan, Huifeng Shui, Shaofeng Guo, Dong MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 |
title | MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 |
title_full | MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 |
title_fullStr | MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 |
title_full_unstemmed | MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 |
title_short | MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1 |
title_sort | microrna-320 enhances radiosensitivity of glioma through down-regulation of sirtuin type 1 by directly targeting forkhead box protein m1 |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772006/ https://www.ncbi.nlm.nih.gov/pubmed/29331678 http://dx.doi.org/10.1016/j.tranon.2017.12.008 |
work_keys_str_mv | AT litengfei microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 AT maji microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 AT hanxinwei microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 AT jiayongxu microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 AT yuanhuifeng microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 AT shuishaofeng microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 AT guodong microrna320enhancesradiosensitivityofgliomathroughdownregulationofsirtuintype1bydirectlytargetingforkheadboxproteinm1 |