miR-125a-3p 通过靶向 MAST3 调控 Wnt/β-catenin 和 NF-κB 通路抑制类风湿关节炎成纤维样滑膜细胞的增殖和炎症反应。

OBJECTIVES

To explore the role and mechanism of miR-125a-3p in rheumatoid arthritis (RA) progression.

METHODS

The RA-tissues and fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) were used in this study. qRT-PCR, western blot and ELISA assay were performed to detect the expression levels of IL-6, IL-β and ΤΝF-α. Dual-luciferase reporter gene assay was used to observe the binding effect of miR-125a-3p and MAST3, and CCK-8 was used to observe the effect of miR-125a-3p on the proliferation of RA-FLS.

RESULTS

miR-125a-3p was significantly downregulated in the RA-tissues and RA-FLS, and miR-125a-3p could inhibit the proliferation and reduce the inflammation response of RA-FLS. Besides, MAST3 was found as a target of miR-125a-3p, and increased MAST3 could reverse the effects of miR-125a-3p on RA-FLS including decreased proliferation, reduced inflammation level and the inactivation of Wnt/β-catenin and NF-κB pathways.

CONCLUSIONS

This study suggests that miR-125a-3p could inactivate the Wnt/β-catenin and NF-κB pathways to reduce the proliferation and inflammation response of RA-FLS via targeting MAST3.

目的

探讨 miR-125a-3p 在类风湿关节炎（RA）进展中的作用和机制。

方法

本研究采用 RA 组织和类风湿关节炎成纤维样滑膜细胞（RA-FLS）。采用 qRT-PCR、western blot 和 ELISA 检测 IL-6、IL-β 和 ΤΝF-α 的表达水平。双荧光素酶报告基因检测 miR-125a-3p 与 MAST3 的结合效应，CCK-8 检测 miR-125a-3p 对 RA-FLS 增殖的影响。

结果

miR-125a-3p 在 RA 组织和 RA-FLS 中表达明显下调，miR-125a-3p 可抑制 RA-FLS 的增殖并降低其炎症反应。此外，MAST3 被发现是 miR-125a-3p 的靶基因，增加 MAST3 可逆转 miR-125a-3p 对 RA-FLS 的作用，包括降低增殖、降低炎症水平以及抑制 Wnt/β-catenin 和 NF-κB 通路的激活。