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microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1
Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a (“miR-19a”, -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a dow...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788617/ https://www.ncbi.nlm.nih.gov/pubmed/29416749 http://dx.doi.org/10.18632/oncotarget.23326 |
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author | Liu, Gang Chen, Feng-Li Ji, Feng Fei, Hao-Dong Xie, Yue Wang, Shou-Guo |
author_facet | Liu, Gang Chen, Feng-Li Ji, Feng Fei, Hao-Dong Xie, Yue Wang, Shou-Guo |
author_sort | Liu, Gang |
collection | PubMed |
description | Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a (“miR-19a”, -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling. |
format | Online Article Text |
id | pubmed-5788617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57886172018-02-07 microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 Liu, Gang Chen, Feng-Li Ji, Feng Fei, Hao-Dong Xie, Yue Wang, Shou-Guo Oncotarget Research Paper Activation of mTOR complex 1 (mTORC1) could protect human osteoblasts from dexamethasone. Tuberous sclerosis complex 1 (TSC1) is mTORC1 upstream inhibitory protein. We demonstrate here that microRNA-19a (“miR-19a”, -3p) targets the 3' untranslated regions of TSC1 mRNA. Expression of miR-19a downregulated TSC1 in OB-6 osteoblastic cells and primary human osteoblasts. miR-19a activated mTORC1 and protected human osteoblasts from dexamethasone. mTORC1 inhibition, by RAD001 or Raptor shRNA, almost completely abolished miR-19a-induced osteoblast cytoprotection against dexamethasone. Knockdown of TSC1 by targeted shRNA similarly induced mTORC1 activation and protected osteoblasts. Moreover, miR-19a activated mTORC1-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited dexamethasone-induced reactive oxygen species production in osteoblasts. Together, miR-19a protects human osteoblasts from dexamethasone possibly via targeting TSC1-mTORC1 signaling. Impact Journals LLC 2017-12-15 /pmc/articles/PMC5788617/ /pubmed/29416749 http://dx.doi.org/10.18632/oncotarget.23326 Text en Copyright: © 2018 Liu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Gang Chen, Feng-Li Ji, Feng Fei, Hao-Dong Xie, Yue Wang, Shou-Guo microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 |
title | microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 |
title_full | microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 |
title_fullStr | microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 |
title_full_unstemmed | microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 |
title_short | microRNA-19a protects osteoblasts from dexamethasone via targeting TSC1 |
title_sort | microrna-19a protects osteoblasts from dexamethasone via targeting tsc1 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788617/ https://www.ncbi.nlm.nih.gov/pubmed/29416749 http://dx.doi.org/10.18632/oncotarget.23326 |
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