Department of Integrated TCM & Western Medicine, Hunan Provincial People's Hospital, Changsha 410005, Hunan, China.
Department of Respiratory Medicine, Hunan Provincial People's Hospital, Changsha 410005, Hunan, China.
J Healthc Eng. 2022 Apr 19;2022:8330659. doi: 10.1155/2022/8330659. eCollection 2022.
The abundance of miR-129-5p was detected in the samples including normal tissues and RA tissues and cell lines including human fibroblast-like synoviocytes (hFLSs) and human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The CCK-8 assay, flow cytometry, Transwell, and ELISA were used to observe the effects of miR-129-5p on the phenotype of RA-FLSs. Moreover, the potential targets of miR-129-5p were identified with TargetScan and dual-luciferase reporter gene assay. Besides, the abundances of the proteins were analyzed with western blot.
Decreased miR-129-5p was observed in RA tissues and cells. Increased miR-129-5p obviously blocked the proliferation, inflammatory stress, and migration and remarkably promoted cellular apoptosis. Moreover, BRD4 was confirmed as targets of miR-129-5p, and BRD4 upregulation could partly rescue the inhibition of miR-129-5p on aggressive behaviors of RA-FLSs. Besides, the finding of this study also proved that upregulated miR-129-5p could impede the NF-B pathway via targeting BRD4.
This study suggests that miR-129-5p suppresses the activation of NF-B pathway to block the progression of RA via targeting BRD4.
检测包括正常组织和 RA 组织以及包括人成纤维样滑膜细胞（hFLSs）和人类风湿关节炎成纤维样滑膜细胞（RA-FLSs）在内的细胞系中 miR-129-5p 的丰度。使用 CCK-8 测定法、流式细胞术、Transwell 和 ELISA 观察 miR-129-5p 对 RA-FLSs 表型的影响。此外，使用 TargetScan 和双荧光素酶报告基因检测法鉴定 miR-129-5p 的潜在靶标。此外，使用 Western blot 分析蛋白质的丰度。
在 RA 组织和细胞中观察到 miR-129-5p 的表达降低。miR-129-5p 的增加明显阻止了增殖、炎症应激和迁移，并显著促进了细胞凋亡。此外，BRD4 被确认为 miR-129-5p 的靶标，BRD4 的上调部分可以挽救 miR-129-5p 对 RA-FLSs 侵袭性行为的抑制作用。此外，本研究的发现还证明，上调的 miR-129-5p 可以通过靶向 BRD4 来抑制 NF-κB 通路。
本研究表明，miR-129-5p 通过靶向 BRD4 抑制 NF-κB 通路的激活来阻止 RA 的进展。
