1. MiR-199a-3p inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via suppressing retinoblastoma 1.
- Author
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Yufan Wangyang, Linhong Yi, Tao Wang, Yanbo Feng, Guangwang Liu, Dongya Li, and Xin Zheng
- Subjects
CELL proliferation ,RHEUMATOID arthritis ,FIBROBLASTS ,RETINOBLASTOMA ,NEUROBLASTOMA - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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