RRC ID 56078
Author Wu J, Fan W, Ma L, Geng X.
Title miR-708-5p promotes fibroblast-like synoviocytes' cell apoptosis and ameliorates rheumatoid arthritis by the inhibition of Wnt3a/β-catenin pathway.
Journal Drug Des Devel Ther
Abstract Aim:MicroRNAs (miRNA) are a class of small, highly conserved noncoding RNA molecules, which contain 18-28 nucleotides and are involved in the regulation of gene expression. It has been proved that microRNAs play a very important role in several key cellular processes, such as cell differentiation, cell cycle progression, and apoptosis, as well as in autoimmune disease. One recently identified miRNA, miR-708-5p, has been demonstrated to have profound roles in suppressing oncogenesis in different types of tumors. However, the role of miR-708-5p in rheumatoid arthritis (RA) remains to be fully elucidated. Therefore, in this study, we are aiming to identify the role of miR-708-5p in RA.
Methods:The expression level of miR-708-5p in synovial tissues of patients with RA is much lower than in non-RA controls. The effects of miR-708-5p on cell apoptosis, colony formation, and migration in fibroblast-like synoviocytes were assessed in MH7A cells.
Results:Results showed that delivery of miR-708-5p mimics into synovial fibroblasts MH7A could induce cell apoptosis and inhibit colony formation and migration. In addition, miR-708-5p mimics significantly inhibit Wnt3a/β-catenin pathway activity both in transcription and protein level, which could be reversed by the addition of R-spondin 1, an activator of Wnt pathway. R-spondin 1 could also reverse the inhibition of cell survival and proliferation, which was induced by miR-708-5p mimics in MH7A. Moreover, injection of miR-708-5p mimics into collagen-induced rat RA model could ameliorate the RA index and decrease Wnt3a/β-catenin expression in rat joint tissues.
Conclusion:Therefore, we concluded that miR-708-5p is likely to be involved in RA pathogenesis via inhibition of Wnt3a/β-catenin pathway.
Volume 12
Pages 3439-3447
Published 2018-10-10
DOI 10.2147/DDDT.S177128
PII dddt-12-3439
PMID 30349197
PMC PMC6186895
MeSH Animals Apoptosis / drug effects* Arthritis, Rheumatoid / drug therapy* Arthritis, Rheumatoid / metabolism Arthritis, Rheumatoid / pathology Cell Line Cell Movement / drug effects Collagen Type II Disease Models, Animal Genetic Therapy Humans Male MicroRNAs / genetics MicroRNAs / pharmacokinetics* Rats Rats, Sprague-Dawley Synoviocytes / drug effects* Synoviocytes / metabolism Synoviocytes / pathology Wnt3A Protein / antagonists & inhibitors* Wnt3A Protein / metabolism beta Catenin / antagonists & inhibitors* beta Catenin / metabolism
IF 3.208
Resource
Human and Animal Cells MH7A(RCB1512)