MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma

Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients’ serum, tumor tissues and OS cell lines. Furthermore, we fo...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Yangbai, He, Nengbin, Dong, Yang, Jiang, Chaoyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041092/
https://www.ncbi.nlm.nih.gov/pubmed/27681638
http://dx.doi.org/10.1038/srep34238
_version_ 1782456343287824384
author Sun, Yangbai
He, Nengbin
Dong, Yang
Jiang, Chaoyin
author_facet Sun, Yangbai
He, Nengbin
Dong, Yang
Jiang, Chaoyin
author_sort Sun, Yangbai
collection PubMed
description Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients’ serum, tumor tissues and OS cell lines. Furthermore, we found that knockdown of miR-24 by its specific inhibitors significantly increased the therapeutic effect of doxorubicin (DOX) on OS cell lines (MG-63 and HOS). Moreover, miR-24 inhibitors resensitized the doxorubicin-resistant MG-63 cells (MG-63/R) and HOS cells (HOS/R) to DOX. As the gene of Bcl-2 interacting mediator of cell death (BIM) was proved to be a target of miR-24 in MG-63/R cells, we further observed that the miR-24 inhibitors promoted the DOX-induced apoptosis via mitochondrial pathway. In addition, results of immunoprecipitation showed the release of second mitochondria derived activator of caspase/ direct IAP binding protein with low pI (Smac/DIABLO) abolished the biological activity of X-linked inhibitor of apoptosis protein (XIAP) by binding with it, which subsequently induced the activation of caspase 9, 7 and 3. In summary, those results strongly suggest that the miR-24-BIM-Smac/DIABLO axis might be a novel target for the treatment of OS.
format Online
Article
Text
id pubmed-5041092
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-50410922016-09-30 MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma Sun, Yangbai He, Nengbin Dong, Yang Jiang, Chaoyin Sci Rep Article Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients’ serum, tumor tissues and OS cell lines. Furthermore, we found that knockdown of miR-24 by its specific inhibitors significantly increased the therapeutic effect of doxorubicin (DOX) on OS cell lines (MG-63 and HOS). Moreover, miR-24 inhibitors resensitized the doxorubicin-resistant MG-63 cells (MG-63/R) and HOS cells (HOS/R) to DOX. As the gene of Bcl-2 interacting mediator of cell death (BIM) was proved to be a target of miR-24 in MG-63/R cells, we further observed that the miR-24 inhibitors promoted the DOX-induced apoptosis via mitochondrial pathway. In addition, results of immunoprecipitation showed the release of second mitochondria derived activator of caspase/ direct IAP binding protein with low pI (Smac/DIABLO) abolished the biological activity of X-linked inhibitor of apoptosis protein (XIAP) by binding with it, which subsequently induced the activation of caspase 9, 7 and 3. In summary, those results strongly suggest that the miR-24-BIM-Smac/DIABLO axis might be a novel target for the treatment of OS. Nature Publishing Group 2016-09-29 /pmc/articles/PMC5041092/ /pubmed/27681638 http://dx.doi.org/10.1038/srep34238 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sun, Yangbai
He, Nengbin
Dong, Yang
Jiang, Chaoyin
MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma
title MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma
title_full MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma
title_fullStr MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma
title_full_unstemmed MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma
title_short MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma
title_sort mir-24-bim-smac/diablo axis controls the sensitivity to doxorubicin treatment in osteosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041092/
https://www.ncbi.nlm.nih.gov/pubmed/27681638
http://dx.doi.org/10.1038/srep34238
work_keys_str_mv AT sunyangbai mir24bimsmacdiabloaxiscontrolsthesensitivitytodoxorubicintreatmentinosteosarcoma
AT henengbin mir24bimsmacdiabloaxiscontrolsthesensitivitytodoxorubicintreatmentinosteosarcoma
AT dongyang mir24bimsmacdiabloaxiscontrolsthesensitivitytodoxorubicintreatmentinosteosarcoma
AT jiangchaoyin mir24bimsmacdiabloaxiscontrolsthesensitivitytodoxorubicintreatmentinosteosarcoma