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Research Paper|Volume 12, Issue 14|pp 14376—14390

MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes

Hua Wei1, Qin Wu1, Yumeng Shi2, Aishu Luo3, Shiyu Lin2, Xiaoke Feng4, Jintao Jiang4, Miaojia Zhang2, Fang Wang5, Wenfeng Tan2
  • 1Division of Rheumatology, Clinical Medical College, Yangzhou University, Jiangsu Province, China
  • 2Division of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China
  • 3Division of Rheumatology, The First People’s Hospital of Yancheng, Jiangsu Province, China
  • 4Institute of Integrated Chinese and Western Medicine, Nanjing Medical University, Jiangsu Province, China
  • 5Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China
* Equal contribution
Received: February 21, 2020Accepted: May 27, 2020Published: July 17, 2020
https://doi.org/10.18632/aging.103480

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.

Abstract

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.