Department of Rheumatology, the First People's Hospital of Wenling, Wenling, 317500 Zhejiang, China.
Department of laboratory, the First People's Hospital of Wenling, Wenling, 317500 Zhejiang, China.
Biosci Rep. 2020 Jan 31;40(1). doi: 10.1042/BSR20191900.
Rheumatoid arthritis (RA), a chronic systemic disease, is featured with inflammatory synovitis, which can lead to destruction on bone and cartilage and even cause disability. Emerging studies demonstrated that Fibroblast-like synoviocytes (FLS) is a vital cellular participant in RA progression. Long non-coding RNAs (lncRNAs) are also reported to participate in the pathogenesis of RA. In our present study, lncRNA microarray analysis was applied to screen out lncRNAs differentially expressed in RA FLS. Among which, cytoskeleton regulator RNA (LINC00152) presented biggest fold change. Gain- or loss-of function assays were further carried out in RA FLS, and the results revealed that LINC00152 promoted proliferation but induced apoptosis in RA FLS. Furthermore, up-regulation of LINC00152 may induce promotion of Wnt/β-catenin signaling pathway in RA FLS. Mechanistically, we found that forkhead box M1 (FOXM1) transcriptionally activated LINC00152 in RA FLS. Additionally, LINC00152 positively regulated FOXM1 via sponging miR-1270. In conclusion, the present study focused on elucidating the function of FOXM1/LINC00152 positive feedback loop in RA FLS and its association with Wnt/β-catenin signaling.
类风湿关节炎（RA）是一种慢性系统性疾病，其特征为炎症性滑膜炎，可导致骨和软骨破坏，甚至导致残疾。新兴研究表明，成纤维样滑膜细胞（FLS）是 RA 进展的重要细胞参与者。长链非编码 RNA（lncRNA）也被报道参与 RA 的发病机制。在本研究中，应用 lncRNA 微阵列分析筛选出 RA FLS 中差异表达的 lncRNA。其中，细胞骨架调节 RNA（LINC00152）的变化倍数最大。在 RA FLS 中进一步进行了增益或缺失功能测定，结果表明 LINC00152 促进 RA FLS 的增殖，但诱导其凋亡。此外，LINC00152 的上调可能在 RA FLS 中诱导 Wnt/β-catenin 信号通路的促进。在机制上，我们发现叉头框 M1（FOXM1）在 RA FLS 中转录激活 LINC00152。此外，LINC00152 通过海绵 miR-1270 正向调节 FOXM1。总之，本研究集中于阐明 FOXM1/LINC00152 正反馈环在 RA FLS 中的功能及其与 Wnt/β-catenin 信号的关联。
