Brucine is a weak alkaline indole alkaloid with wide pharmacological activities and has been identified to protect against rheumatoid arthritis (RA) process. Circular RNAs (circRNAs) are also reported to be involved in the pathogenesis of RA. Here, we aimed to probe the role and mechanism of Brucine and circ_0139658 in RA progression. The fibroblast‐like synoviocytes of RA (RA‐FLSs) were isolated for functional analysis. Cell proliferation, apoptosis, invasion, migration, as well as inflammatory response were evaluated by CCK‐8 assay, EdU assay, flow cytometry, transwell assay, and ELISA analysis, respectively. qRT‐PCR and western blotting analyses were utilized to measure the levels of genes and proteins. The binding between miR‐653‐5p and circ_0139658 or Yin Yang 1 (YY1), was verified using dual‐luciferase reporter and RNA pull‐down assays. Brucine suppressed the proliferation, migration, and invasion of RA‐FLSs, and alleviated inflammation by reducing the release of pro‐inflammatory factors and macrophage M1 polarization. RA‐FLSs showed increased circ_0139658 and YY1 levels and decreased miR‐653‐5p levels. Circ_0139658 is directly bound to miR‐653‐5p to regulate YY1 expression. Brucine treatment suppressed circ_0139658 and YY1 expression but increased YY1 expression in RA‐FLSs. Functionally, circ_0139658 overexpression reversed the suppressing effects of Brucine on RA‐FLS dysfunction and inflammation. Moreover, circ_0139658 silencing alleviated the dysfunction and inflammation in RA‐FLSs, which were reverted by YY1 overexpression. Brucine suppressed the proliferation, migration, invasion, and inflammation in RA‐FLSs by decreasing YY1 via circ_0139658/miR‐653‐5p axis.

中文翻译：

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马钱子碱通过调节类风湿性关节炎期间的 YY1 减轻成纤维细胞样滑膜细胞功能障碍和炎症

马钱子碱是一种弱碱性吲哚生物碱，具有广泛的药理活性，已被确定可以预防类风湿关节炎 (RA) 过程。据报道，环状 RNA (circRNA) 也参与 RA 的发病机制。在这里，我们的目的是探讨马钱子碱和circ_0139658在RA进展中的作用和机制。分离 RA 的成纤维细胞样滑膜细胞 (RA-FLS) 进行功能分析。分别通过CCK-8测定、EdU测定、流式细胞术、Transwell测定和ELISA分析评估细胞增殖、凋亡、侵袭、迁移和炎症反应。qRT-PCR 和蛋白质印迹分析用于测量基因和蛋白质的水平。使用双荧光素酶报告基因和 RNA Pull-down 测定验证了 miR-653-5p 和 circ_0139658 或 Yin Yang 1 (YY1) 之间的结合。马钱子碱抑制 RA-FLS 的增殖、迁移和侵袭，并通过减少促炎因子的释放和巨噬细胞 M1 极化来减轻炎症。RA-FLS 显示 circ_0139658 和 YY1 水平升高，而 miR-653-5p 水平降低。Circ_0139658 直接与 miR-653-5p 结合来调节 YY1 表达。马钱子碱处理抑制了 RA-FLS 中 circ_0139658 和 YY1 的表达，但增加了 YY1 的表达。从功能上讲，circ_0139658 过度表达逆转了马钱子碱对 RA-FLS 功能障碍和炎症的抑制作用。此外，circ_0139658沉默减轻了RA-FLS的功能障碍和炎症，而YY1过表达可恢复这些功能障碍和炎症。马钱子碱通过 circ_0139658/miR-653-5p 轴减少 YY1，抑制 RA-FLS 的增殖、迁移、侵袭和炎症。