Immunology Department, Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, China.
Immunology Department, West China Hospital of Sichuan University, Chengdu, China.
Hum Cell. 2018 Jan;31(1):14-21. doi: 10.1007/s13577-017-0179-5. Epub 2017 Jul 18.
Rheumatoid arthritis (RA) is a systemic and chronic inflammatory disease. Synoviocyte migration and invasion were found to be essential to the pathology of RA. Upregulation of long noncoding RNA ZFAS1 has been observed in cancers and promotes cell migration and invasion. To date, the functions and mechanisms of ZFAS1 in RA have not been revealed. In this study, we analyzed expression pattern of ZFAS1 in RA patients and found that ZFAS1 expression was increased in synovial tissue and fibroblast-like synoviocytes (FLS) from RA patients (RA-FLS) compared with that in healthy donors. Functional assays showed that silence of ZFAS1 suppressed RA-FLS migration and invasion, while overexpression of ZFAS1 showed the opposite effect. Further investigation demonstrated that ZFAS1 directly interacted with miR-27a and decreased miR-27a expression. ZFAS1 promotes RA-FLS migration and invasion in an miR-27a-dependent manner. Taken together, the present study provides the first evidence that ZFAS1 promotes cell migration and invasion through miR-27a in RA-FLS, suggesting that ZFAS1 may be an effective therapeutic target for RA patients.
类风湿关节炎（RA）是一种系统性和慢性炎症性疾病。研究发现，滑膜细胞迁移和侵袭对于 RA 的病理学至关重要。长链非编码 RNA ZFAS1 的表达上调已在癌症中观察到，并促进细胞迁移和侵袭。迄今为止，ZFAS1 在 RA 中的功能和机制尚未被揭示。在本研究中，我们分析了 RA 患者中 ZFAS1 的表达模式，发现与健康供体相比，RA 患者的滑膜组织和滑膜成纤维样细胞（RA-FLS）中 ZFAS1 的表达增加。功能测定表明，ZFAS1 沉默抑制 RA-FLS 的迁移和侵袭，而过表达 ZFAS1 则表现出相反的效果。进一步的研究表明，ZFAS1 可以直接与 miR-27a 相互作用，降低 miR-27a 的表达。ZFAS1 通过 miR-27a 促进 RA-FLS 的迁移和侵袭。综上所述，本研究首次提供了证据表明，ZFAS1 通过 miR-27a 在 RA-FLS 中促进细胞迁移和侵袭，提示 ZFAS1 可能是 RA 患者的有效治疗靶点。
