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MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1
Background Fibroblast-like synoviocytes (FLSs) that line the intimal synovium play a crucial role in the pathogenesis of rheumatoid arthritis (RA). miR-199a-3p is a highly conserved miRNA that has been shown to regulate a variety of growth behaviors in diverse cell types. However, the role of miR-19...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239273/ https://www.ncbi.nlm.nih.gov/pubmed/30352835 http://dx.doi.org/10.1042/BSR20180982 |
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author | Wangyang, Yufan Yi, Linhong Wang, Tao Feng, Yanbo Liu, Guangwang Li, Dongya Zheng, Xin |
author_facet | Wangyang, Yufan Yi, Linhong Wang, Tao Feng, Yanbo Liu, Guangwang Li, Dongya Zheng, Xin |
author_sort | Wangyang, Yufan |
collection | PubMed |
description | Background Fibroblast-like synoviocytes (FLSs) that line the intimal synovium play a crucial role in the pathogenesis of rheumatoid arthritis (RA). miR-199a-3p is a highly conserved miRNA that has been shown to regulate a variety of growth behaviors in diverse cell types. However, the role of miR-199a-3p in RA-FLS is still unknown. Methods Here, we presented the first experimental evidence showing that miR-199a-3p was a critical regulator of RA-FLS function. Results miR-199a-3p expression was significantly reduced in RA-FLS compared with normal FLS. Ectopic expression of miR-199a-3p significantly inhibited RA-FLS proliferation and induced apoptosis, which was demonstrated by an increase in caspase-3 activity and Bax/Bcl-2 ratio. Our bioinformatics analysis identified Retinoblastoma 1 (RB1) gene to be a direct target of miR-199a-3p. In RA-FLS, miR-199a-3p directly targetted the 3′-UTR of RB1 mRNA and suppressed endogenous RB1 expression, whereas miR-199a-3p-resistant variant of RB1 was not affected. Silencing RB1 decreased cell proliferation and promoted apoptosis in RA-FLS, an effect comparable with miR-199a-3p overexpression. Enforced expression of RB1 partially restored cell proliferation and attenuated apoptosis in miR-199a-3p-overexpressing RA-FLSs. Conclusion In summary, miR-199a-3p is down-regulated in RA-FLS, and miR-199a-3p inhibits proliferation and induces apoptosis in RA-FLS, partially via targetting RB1. The miR-199a-3p/RB1 pathway may represent a new therapeutic target for RA. |
format | Online Article Text |
id | pubmed-6239273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62392732018-11-28 MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 Wangyang, Yufan Yi, Linhong Wang, Tao Feng, Yanbo Liu, Guangwang Li, Dongya Zheng, Xin Biosci Rep Research Articles Background Fibroblast-like synoviocytes (FLSs) that line the intimal synovium play a crucial role in the pathogenesis of rheumatoid arthritis (RA). miR-199a-3p is a highly conserved miRNA that has been shown to regulate a variety of growth behaviors in diverse cell types. However, the role of miR-199a-3p in RA-FLS is still unknown. Methods Here, we presented the first experimental evidence showing that miR-199a-3p was a critical regulator of RA-FLS function. Results miR-199a-3p expression was significantly reduced in RA-FLS compared with normal FLS. Ectopic expression of miR-199a-3p significantly inhibited RA-FLS proliferation and induced apoptosis, which was demonstrated by an increase in caspase-3 activity and Bax/Bcl-2 ratio. Our bioinformatics analysis identified Retinoblastoma 1 (RB1) gene to be a direct target of miR-199a-3p. In RA-FLS, miR-199a-3p directly targetted the 3′-UTR of RB1 mRNA and suppressed endogenous RB1 expression, whereas miR-199a-3p-resistant variant of RB1 was not affected. Silencing RB1 decreased cell proliferation and promoted apoptosis in RA-FLS, an effect comparable with miR-199a-3p overexpression. Enforced expression of RB1 partially restored cell proliferation and attenuated apoptosis in miR-199a-3p-overexpressing RA-FLSs. Conclusion In summary, miR-199a-3p is down-regulated in RA-FLS, and miR-199a-3p inhibits proliferation and induces apoptosis in RA-FLS, partially via targetting RB1. The miR-199a-3p/RB1 pathway may represent a new therapeutic target for RA. Portland Press Ltd. 2018-11-14 /pmc/articles/PMC6239273/ /pubmed/30352835 http://dx.doi.org/10.1042/BSR20180982 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Wangyang, Yufan Yi, Linhong Wang, Tao Feng, Yanbo Liu, Guangwang Li, Dongya Zheng, Xin MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
title | MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
title_full | MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
title_fullStr | MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
title_full_unstemmed | MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
title_short | MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
title_sort | mir-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239273/ https://www.ncbi.nlm.nih.gov/pubmed/30352835 http://dx.doi.org/10.1042/BSR20180982 |
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