Department of Nephrology, Western Theater General Hospital, Chengdu, Sichuan, China.
Department of Pathology, Weifang Traditional Chinese Hospital, Weifang, Shandong, China.
J Orthop Surg Res. 2021 May 8;16(1):302. doi: 10.1186/s13018-021-02432-3.
Previous study showed that circular RNA Absent-Small-Homeotic-2--Like protein (circASH2L) was higher in rheumatoid arthritis (RA) patients. However, the roles and mechanisms of circASH2L in RA progression remain unclear.
Levels analysis was conducted using western blot and qRT-PCR. The proliferation, apoptosis, cell cycle progression, migration, invasiveness, and inflammation of RA fibroblast-like synoviocytes (RA-FLSs) were determined via MTT, flow cytometry, western blot, transwell, and ELISA assays.
CircASH2L knockdown in RA-FLSs suppressed cell proliferative, migratory, and invasive capacities, triggered cell cycle arrest, promoted apoptosis, and inhibited inflammation. Mechanistically, circASH2L targeted miR-129-5p, and repression of miR-129-5p abolished the functions of circASH2L silencing on the growth, motility, and inflammation of RA-FLSs. Besides, miR-129-5p was found to directly target HIPK2, and suppressed the tumor-like biologic behaviors and inflammation of RA-FLSs via regulating HIPK2. Importantly, we proved that circASH2L could modulate HIPK2 expression via miR-129-5p.
CircASH2L promoted RA-FLS growth, motility, and inflammation through miR-129-5p/HIPK2 axis.
先前的研究表明，环状 RNA 缺失小同源异型框蛋白 2 样蛋白（circASH2L）在类风湿关节炎（RA）患者中水平升高。然而，circASH2L 在 RA 进展中的作用和机制尚不清楚。
采用 Western blot 和 qRT-PCR 进行水平分析。通过 MTT、流式细胞术、Western blot、Transwell 和 ELISA 测定 RA 成纤维样滑膜细胞（RA-FLS）的增殖、凋亡、细胞周期进程、迁移、侵袭和炎症。
在 RA-FLS 中敲低 circASH2L 抑制了细胞的增殖、迁移和侵袭能力，引发了细胞周期停滞，促进了细胞凋亡，并抑制了炎症。机制上，circASH2L 靶向 miR-129-5p，抑制 miR-129-5p 消除了 circASH2L 沉默对 RA-FLS 生长、迁移和炎症的作用。此外，发现 miR-129-5p 可直接靶向 HIPK2，并通过调节 HIPK2 抑制 RA-FLS 的肿瘤样生物学行为和炎症。重要的是，我们证明了 circASH2L 可以通过 miR-129-5p 调节 HIPK2 的表达。
circASH2L 通过 miR-129-5p/HIPK2 轴促进 RA-FLS 的生长、迁移和炎症。
