miR-449a inhibits cell proliferation, migration, and inflammation by regulating high-mobility group box protein 1 and forms a mutual inhibition loop with Yin Yang 1 in rheumatoid arthritis fibroblast-like synoviocytes

• Main Authors: Yongsong Cai, Congshan Jiang, Jialin Zhu, Ke Xu, Xiaoyu Ren, Lin Xu, Peijing Hu, Bo Wang, Qiling Yuan, Yuanxu Guo, Jian Sun, Peng Xu, Yusheng Qiu
• Format: Article
• Language: English
• Published: BMC 2019-06-01
• Series: Arthritis Research & Therapy
• Subjects: miR-449a; Rheumatoid arthritis; Fibroblast-like synoviocytes; Proliferation; Inflammation; High-mobility group box protein 1
• Online Access: http://link.springer.com/article/10.1186/s13075-019-1920-0

Abstract Background We previously found that high-mobility group box protein 1 (HMGB1) promoted cell proliferation, migration, invasion, and autophagy in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), but little is known about its regulatory mechanism. The aim of this study was to investigate the regulatory mechanism of HMGB1 at the posttranscription level. Methods Real-time qPCR, CCK-8 cell proliferation assay, transwell cell migration assay, enzyme-linked immunosorbent assay (ELISA), and western blotting were used in this study. The targeting relationship between miRNA and mRNA was presented by the luciferase reporter assay. Results MiR-449a was downregulated in RA synovial tissue and inhibited RA-FLS proliferation, migration, and IL-6 production. MiR-449a directly targeted HMGB1 and inhibited its expression. Yin Yang 1(YY1) negatively regulated miR-449a expression and formed a mutual inhibition loop in RA-FLS. MiR-449a inhibited TNFα-mediated HMGB1 and YY1 overexpression and IL-6 production. Conclusions Our results reveal the regulatory mechanism of HMGB1 in RA and demonstrate that miR-449a is a crucial molecule in RA pathogenesis and a suitable candidate for miRNA replacement therapies in RA.