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LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway

Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we perform...

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Autores principales: Li, Guoqing, Liu, Ying, Meng, Fanru, Xia, Zhongbin, Wu, Xia, Fang, Yuxuan, Zhang, Chunwang, Zhang, Yu, Liu, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787440/
https://www.ncbi.nlm.nih.gov/pubmed/31411001
http://dx.doi.org/10.1111/jcmm.14591
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author Li, Guoqing
Liu, Ying
Meng, Fanru
Xia, Zhongbin
Wu, Xia
Fang, Yuxuan
Zhang, Chunwang
Zhang, Yu
Liu, Dan
author_facet Li, Guoqing
Liu, Ying
Meng, Fanru
Xia, Zhongbin
Wu, Xia
Fang, Yuxuan
Zhang, Chunwang
Zhang, Yu
Liu, Dan
author_sort Li, Guoqing
collection PubMed
description Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we performed a series of experiments using RA samples. We found that MEG3 was downregulated in the fibroblast‐like synoviocytes of RA patients (RA‐FLS), in comparison with healthy subjects. MEG3 was also down‐regulated evidently in lipopolysaccharide (LPS)‐treated chondrocyte. As part of our experiments, MEG3 was overexpressed in chondrocyte by transfection with lentivirus containing sequences encoding MEG3. In addition, in presence of LPS, reductions were identified not only in the cell proliferation, but also in the generation of interleukin‐23 (IL‐23), which, however were reversed in the lentivirus (containing MEG3‐encoding sequences)‐transfected chondrocytes. Up‐regulated MEG3 resulted in an increase the level of Ki67. Moreover, MEG3 was negatively correlated with miR‐141, and miR‐141 was up‐regulated in LPS‐treated chondrocyte. Inhibitory effects of MEG3 overexpression, mentioned above, were partially abolished by overexpressed miR‐141. Further, animal experiment also showed the inhibitory effect of MEG3 in overexpression on the AKT/mTOR signaling pathway. In‐vivoexperiments also showed that cell proliferation was facilitated by MEG3 overexpression with inhibited inflammation. In summary, the protective role of MEG3 in RA was proved to be exerted by the increase in the rate of proliferation, which might correlate to the regulatory role of miR‐141 and AKT/mTOR signal pathway, suggesting that MEG3 holds great promise as a therapeutic strategy for RA.
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spelling pubmed-67874402019-10-17 LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway Li, Guoqing Liu, Ying Meng, Fanru Xia, Zhongbin Wu, Xia Fang, Yuxuan Zhang, Chunwang Zhang, Yu Liu, Dan J Cell Mol Med Short Communications Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we performed a series of experiments using RA samples. We found that MEG3 was downregulated in the fibroblast‐like synoviocytes of RA patients (RA‐FLS), in comparison with healthy subjects. MEG3 was also down‐regulated evidently in lipopolysaccharide (LPS)‐treated chondrocyte. As part of our experiments, MEG3 was overexpressed in chondrocyte by transfection with lentivirus containing sequences encoding MEG3. In addition, in presence of LPS, reductions were identified not only in the cell proliferation, but also in the generation of interleukin‐23 (IL‐23), which, however were reversed in the lentivirus (containing MEG3‐encoding sequences)‐transfected chondrocytes. Up‐regulated MEG3 resulted in an increase the level of Ki67. Moreover, MEG3 was negatively correlated with miR‐141, and miR‐141 was up‐regulated in LPS‐treated chondrocyte. Inhibitory effects of MEG3 overexpression, mentioned above, were partially abolished by overexpressed miR‐141. Further, animal experiment also showed the inhibitory effect of MEG3 in overexpression on the AKT/mTOR signaling pathway. In‐vivoexperiments also showed that cell proliferation was facilitated by MEG3 overexpression with inhibited inflammation. In summary, the protective role of MEG3 in RA was proved to be exerted by the increase in the rate of proliferation, which might correlate to the regulatory role of miR‐141 and AKT/mTOR signal pathway, suggesting that MEG3 holds great promise as a therapeutic strategy for RA. John Wiley and Sons Inc. 2019-08-14 2019-10 /pmc/articles/PMC6787440/ /pubmed/31411001 http://dx.doi.org/10.1111/jcmm.14591 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 Short Communications
Li, Guoqing
Liu, Ying
Meng, Fanru
Xia, Zhongbin
Wu, Xia
Fang, Yuxuan
Zhang, Chunwang
Zhang, Yu
Liu, Dan
LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway
title LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway
title_full LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway
title_fullStr LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway
title_full_unstemmed LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway
title_short LncRNA MEG3 inhibits rheumatoid arthritis through miR‐141 and inactivation of AKT/mTOR signalling pathway
title_sort lncrna meg3 inhibits rheumatoid arthritis through mir‐141 and inactivation of akt/mtor signalling pathway
topic Short Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787440/
https://www.ncbi.nlm.nih.gov/pubmed/31411001
http://dx.doi.org/10.1111/jcmm.14591
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