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Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis
The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lnc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911397/ https://www.ncbi.nlm.nih.gov/pubmed/36759677 http://dx.doi.org/10.1038/s41598-023-29546-4 |
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author | Wang, Ziyu Zhang, Hengshuo Li, Qinghui Zhang, Lu Chen, Lu Wang, Hongliang Chen, Yunzhen |
author_facet | Wang, Ziyu Zhang, Hengshuo Li, Qinghui Zhang, Lu Chen, Lu Wang, Hongliang Chen, Yunzhen |
author_sort | Wang, Ziyu |
collection | PubMed |
description | The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis. |
format | Online Article Text |
id | pubmed-9911397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99113972023-02-11 Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis Wang, Ziyu Zhang, Hengshuo Li, Qinghui Zhang, Lu Chen, Lu Wang, Hongliang Chen, Yunzhen Sci Rep Article The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis. Nature Publishing Group UK 2023-02-09 /pmc/articles/PMC9911397/ /pubmed/36759677 http://dx.doi.org/10.1038/s41598-023-29546-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Ziyu Zhang, Hengshuo Li, Qinghui Zhang, Lu Chen, Lu Wang, Hongliang Chen, Yunzhen Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
title | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
title_full | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
title_fullStr | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
title_full_unstemmed | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
title_short | Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis |
title_sort | long non-coding rna kcnq1ot1 alleviates postmenopausal osteoporosis by modulating mir-421-3p/mtor axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911397/ https://www.ncbi.nlm.nih.gov/pubmed/36759677 http://dx.doi.org/10.1038/s41598-023-29546-4 |
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