Research Paper Advance Articles
MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes
- 1 Division of Rheumatology, Clinical Medical College, Yangzhou University, Jiangsu Province, China
- 2 Division of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China
- 3 Division of Rheumatology, The First People’s Hospital of Yancheng, Jiangsu Province, China
- 4 Institute of Integrated Chinese and Western Medicine, Nanjing Medical University, Jiangsu Province, China
- 5 Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China
Received: February 21, 2020 Accepted: May 27, 2020 Published: July 17, 2020https://doi.org/10.18632/aging.103480
How to Cite
Copyright © 2020 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fibroblast-like synoviocytes (FLSs) are key effector cells in the pathogenesis of rheumatoid arthritis (RA) and display a unique aggressive tumor-like phenotype with remarkable hyperplasia, increased cell migration and invasion. How FLSs undergo these changes in RA remains unknown. We previously reported a novel function of transcription factor SOX5 in RA-FLSs that promote cell migration and invasion. In this study, we found that miR-15a/16 directly targets the SOX5 3’UTR and suppresses SOX5 expression. Moreover, miR-15a/16 is significantly down-regulated in RA-FLSs, which negatively correlates with SOX5 expression. Transfection with miR-15a/16 mimics in RA-FLSs inhibits cell migration, invasion, IL-1β and TNFα expression. Overexpression SOX5 in RA-FLSs decreases miR-15a/16 expression and rescues miR-15a/16-mediated inhibitory effect. Furthermore, RA patients with the lower baseline serum miR-15a/16 level present poor response of 3 months disease-modifying antirheumatic drugs (DMARDs) therapy. Collectively, this study reveals that miR-15a/16/SOX5 axis functions as a key driver of RA-FLSs invasion, migration and inflammatory response in a mutual negative feedback loop and correlates with DMARDs treatment response in RA.