MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes
MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes
复制标题
MicroRNA-15a/16/SOX5轴促进类风湿性关节炎成纤维细胞样滑膜细胞的迁移、侵袭和炎症反应
DOI：
10.18632/aging.103480
复制
发表时间：
2020
期刊：
影响因子：
5.2
通讯作者：
Tan Wenfeng
中科院分区：
文献类型：
--
作者：
Wei Hua;Wu Qin;Shi Yumeng;Luo Aishu;Lin Shiyu;Feng Xiaoke;Jiang Jintao;Zhang Miaojia;Wang Fang;Tan Wenfeng
成纤维样滑膜细胞（FLS）是类风湿性关节炎（RA）发病机制中的关键效应细胞，并表现出独特的侵袭性肿瘤样表型，具有显着的增生、细胞迁移和侵袭增加。 FLS 如何在 RA 中经历这些变化仍然未知。我们之前报道了转录因子 SOX5 在 RA-FLS 中促进细胞迁移和侵袭的新功能。在这项研究中，我们发现miR-15a/16直接靶向SOX5 3'UTR并抑制SOX5表达。此外，miR-15a/16 在 RA-FLS 中显着下调，这与 SOX5 表达负相关。在 RA-FLS 中转染 miR-15a/16 模拟物可抑制细胞迁移、侵袭、IL-1β 和 TNFα 表达。 RA-FLS 中过度表达 SOX5 会降低 miR-15a/16 表达并挽救 miR-15a/16 介导的抑制作用。此外，基线血清 miR-15a/16 水平较低的 RA 患者对 3 个月的疾病缓解抗风湿药物 (DMARD) 治疗反应不佳。总的来说，这项研究揭示了 miR-15a/16/SOX5 轴在相互负反馈循环中作为 RA-FLS 侵袭、迁移和炎症反应的关键驱动因素，并与 RA 的 DMARD 治疗反应相关。
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.