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LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis
BACKGROUND: Many studies have reported that long noncoding RNAs (lncRNAs) could act as sponges for microRNAs (miRNAs) and play important roles in the regulation of osteoarthritis (OA). Yet, the underlying mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OA are...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600894/ https://www.ncbi.nlm.nih.gov/pubmed/31304004 http://dx.doi.org/10.1186/s13578-019-0302-2 |
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author | Zhang, Ying Wang, Fuyou Chen, Guangxing He, Rui Yang, Liu |
author_facet | Zhang, Ying Wang, Fuyou Chen, Guangxing He, Rui Yang, Liu |
author_sort | Zhang, Ying |
collection | PubMed |
description | BACKGROUND: Many studies have reported that long noncoding RNAs (lncRNAs) could act as sponges for microRNAs (miRNAs) and play important roles in the regulation of osteoarthritis (OA). Yet, the underlying mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OA are still unclear. Therefore, we aimed to explore the regulation mechanisms of MALAT1 in OA procession. METHODS: IL-1β treatment in chondrocyte was used to mimic OA in vitro. MALAT1, miR-150-5p and AKT3 expression levels were detected via qRT-PCR. The protein levels of AKT3, MMP-13, ADAMTS-5, Bax, Bcl-2, cleaved-PARP, collagen II and aggracan were measured by western blot. MTT assay was performed to detect cell proliferation ability. The apoptosis of chondrocytes was determined using flow cytometry and western blot. Luciferase assay and RNA immunoprecipitation (RIP) assays were used to confirm the relationship among MALAT1, miR-150-5p and AKT3. RESULTS: In our study, MALAT1 and AKT3 were upregulated while miR-150-5p was downregulated in OA in vitro and vivo. The level of miR-150-5p was negatively correlated with that of MALAT1 or AKT3. More importantly, overexpression of MALAT1 promoted the expression of AKT3 by negatively regulating miR-150-5p. MALAT1 knockdown inhibited cell proliferation, promoted apoptosis, increased MMP-13, ADAMTS-5 expression and decreased collagen II, aggracan expression in IL-1β treated chondrocytes. MALAT1 upregulation or AKT3 overexpression enhanced proliferation, inhibited apoptosis and extracellular matrix (ECM) degradation, which was undermined by overexpression of miR-150-5p. By contrast, miR-150-5p depletion rescued the effect of MALAT1 downregulation or loss of AKT3 on IL-1β-stimulated chondrocytes. CONCLUSION: MALAT1 was responsible for cell proliferation, apoptosis, and ECM degradation via miR-150-5p/AKT3 axis. |
format | Online Article Text |
id | pubmed-6600894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66008942019-07-12 LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis Zhang, Ying Wang, Fuyou Chen, Guangxing He, Rui Yang, Liu Cell Biosci Review BACKGROUND: Many studies have reported that long noncoding RNAs (lncRNAs) could act as sponges for microRNAs (miRNAs) and play important roles in the regulation of osteoarthritis (OA). Yet, the underlying mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OA are still unclear. Therefore, we aimed to explore the regulation mechanisms of MALAT1 in OA procession. METHODS: IL-1β treatment in chondrocyte was used to mimic OA in vitro. MALAT1, miR-150-5p and AKT3 expression levels were detected via qRT-PCR. The protein levels of AKT3, MMP-13, ADAMTS-5, Bax, Bcl-2, cleaved-PARP, collagen II and aggracan were measured by western blot. MTT assay was performed to detect cell proliferation ability. The apoptosis of chondrocytes was determined using flow cytometry and western blot. Luciferase assay and RNA immunoprecipitation (RIP) assays were used to confirm the relationship among MALAT1, miR-150-5p and AKT3. RESULTS: In our study, MALAT1 and AKT3 were upregulated while miR-150-5p was downregulated in OA in vitro and vivo. The level of miR-150-5p was negatively correlated with that of MALAT1 or AKT3. More importantly, overexpression of MALAT1 promoted the expression of AKT3 by negatively regulating miR-150-5p. MALAT1 knockdown inhibited cell proliferation, promoted apoptosis, increased MMP-13, ADAMTS-5 expression and decreased collagen II, aggracan expression in IL-1β treated chondrocytes. MALAT1 upregulation or AKT3 overexpression enhanced proliferation, inhibited apoptosis and extracellular matrix (ECM) degradation, which was undermined by overexpression of miR-150-5p. By contrast, miR-150-5p depletion rescued the effect of MALAT1 downregulation or loss of AKT3 on IL-1β-stimulated chondrocytes. CONCLUSION: MALAT1 was responsible for cell proliferation, apoptosis, and ECM degradation via miR-150-5p/AKT3 axis. BioMed Central 2019-07-01 /pmc/articles/PMC6600894/ /pubmed/31304004 http://dx.doi.org/10.1186/s13578-019-0302-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Zhang, Ying Wang, Fuyou Chen, Guangxing He, Rui Yang, Liu LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis |
title | LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis |
title_full | LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis |
title_fullStr | LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis |
title_full_unstemmed | LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis |
title_short | LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis |
title_sort | lncrna malat1 promotes osteoarthritis by modulating mir-150-5p/akt3 axis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600894/ https://www.ncbi.nlm.nih.gov/pubmed/31304004 http://dx.doi.org/10.1186/s13578-019-0302-2 |
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