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Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1
Chemotherapy resistance is one of the major challenges for the treatment of osteosarcoma (OS). The potential roles of oestrogenic signals in the chemoresistance of OS cells were investigated. As compare to the parental cells, the doxorubicin and cisplatin (CDDP) resistant OS cells had greater levels...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378180/ https://www.ncbi.nlm.nih.gov/pubmed/30609256 http://dx.doi.org/10.1111/jcmm.14123 |
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author | Chen, Yantao Zhang, Kunshui Li, Yang Guo, Ruilian Zhang, Kelin Zhong, Guifang He, Qing |
author_facet | Chen, Yantao Zhang, Kunshui Li, Yang Guo, Ruilian Zhang, Kelin Zhong, Guifang He, Qing |
author_sort | Chen, Yantao |
collection | PubMed |
description | Chemotherapy resistance is one of the major challenges for the treatment of osteosarcoma (OS). The potential roles of oestrogenic signals in the chemoresistance of OS cells were investigated. As compare to the parental cells, the doxorubicin and cisplatin (CDDP) resistant OS cells had greater levels of oestrogen‐related receptors alpha (ERRα). Targeted inhibition of ERRα by its specific siRNAs or inverse agonist XCT‐790 can restore the sensitivity of OS resistant cells to chemotherapy. This might be due to that si‐ERRα can decrease the expression of P‐glycoprotein (P‐gp, encoded by ABCB1), one important ABC membrane transporter for drug efflux. XCT‐790 can decrease the transcription and mRNA stability of ABCB1, while had no effect on protein stability of P‐gp. ERRα can bind to the transcription factor of SP3 to increase the transcription of ABCB1. Furthermore, XCT‐790 treatment decreased the expression of miR‐9, which can bind to the 3′UTR of ABCB1 and trigger its decay. Collectively, we found that ERRα can regulate the chemoresistance of OS cells via regulating the transcription and mRNA stability of ABCB1. Targeted inhibition of ERRα might be a potential approach for OS therapy. |
format | Online Article Text |
id | pubmed-6378180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63781802019-03-01 Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 Chen, Yantao Zhang, Kunshui Li, Yang Guo, Ruilian Zhang, Kelin Zhong, Guifang He, Qing J Cell Mol Med Original Articles Chemotherapy resistance is one of the major challenges for the treatment of osteosarcoma (OS). The potential roles of oestrogenic signals in the chemoresistance of OS cells were investigated. As compare to the parental cells, the doxorubicin and cisplatin (CDDP) resistant OS cells had greater levels of oestrogen‐related receptors alpha (ERRα). Targeted inhibition of ERRα by its specific siRNAs or inverse agonist XCT‐790 can restore the sensitivity of OS resistant cells to chemotherapy. This might be due to that si‐ERRα can decrease the expression of P‐glycoprotein (P‐gp, encoded by ABCB1), one important ABC membrane transporter for drug efflux. XCT‐790 can decrease the transcription and mRNA stability of ABCB1, while had no effect on protein stability of P‐gp. ERRα can bind to the transcription factor of SP3 to increase the transcription of ABCB1. Furthermore, XCT‐790 treatment decreased the expression of miR‐9, which can bind to the 3′UTR of ABCB1 and trigger its decay. Collectively, we found that ERRα can regulate the chemoresistance of OS cells via regulating the transcription and mRNA stability of ABCB1. Targeted inhibition of ERRα might be a potential approach for OS therapy. John Wiley and Sons Inc. 2019-01-04 2019-03 /pmc/articles/PMC6378180/ /pubmed/30609256 http://dx.doi.org/10.1111/jcmm.14123 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Chen, Yantao Zhang, Kunshui Li, Yang Guo, Ruilian Zhang, Kelin Zhong, Guifang He, Qing Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 |
title | Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 |
title_full | Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 |
title_fullStr | Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 |
title_full_unstemmed | Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 |
title_short | Oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1 |
title_sort | oestrogen‐related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of abcb1 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378180/ https://www.ncbi.nlm.nih.gov/pubmed/30609256 http://dx.doi.org/10.1111/jcmm.14123 |
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