Department of Rheumatology & Clinical Immunology, Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Sci Rep. 2024 Sep 30;14(1):22608. doi: 10.1038/s41598-024-73607-1.
Accumulated data implicate that long noncoding RNA (lncRNA) plays a pivotal role in rheumatoid arthritis (RA), potentially serving as a competitive endogenous RNA (ceRNA) for microRNAs (miRNAs). The lncRNA myocardial infarction-associated transcript (MIAT) has been demonstrated to regulate inflammation. However, the role of MIAT in the inflammation of RA remains inadequately explored. This study aims to elucidate MIAT's role in the inflammation of lipopolysaccharide (LPS)-induced macrophages and to uncover the underlying molecular mechanisms. We observed heightened MIAT expression in LPS-induced J774A.1 cells and collagen-induced arthritis mouse models, in contrast to the expression pattern of miR-30a-5p. Silencing MIAT resulted in increased expression of the inflammatory cytokines IL-1β and TNF-α. Simultaneously, MIAT interference significantly impeded macrophage autophagy, evidenced by decreased expression of autophagy-related markers LC3-II and Beclin-1, alongside increased levels of p62 in LPS-induced J774A.1 cells. Notably, MIAT functioned as a ceRNA, sponging miR-30a-5p and exerting a negative regulatory influence on its expression. SOCS1 emerged as a target of miR-30a-5p, modulated by MIAT. Mechanistically, inhibiting miR-30a-5p reversed the impact of MIAT deficiency in promoting LPS-induced inflammation, while SOCS1 knockdown countered the cytokine inhibitory effect induced by silencing miR-30a-5p. In summary, this study indicates that lncRNA MIAT suppresses inflammation in LPS-induced J774A.1 macrophages by stimulating autophagy through the miR-30a-5p/SOCS1 axis. This suggests that MIAT holds promise as a potential therapeutic target for RA inflammation.
累积数据表明，长链非编码 RNA（lncRNA）在类风湿关节炎（RA）中发挥关键作用，可能作为 microRNAs（miRNAs）的竞争性内源性 RNA（ceRNA）。lncRNA 心肌梗塞相关转录物（MIAT）已被证明可调节炎症。然而，MIAT 在 RA 炎症中的作用仍未得到充分探讨。本研究旨在阐明 MIAT 在脂多糖（LPS）诱导的巨噬细胞炎症中的作用，并揭示潜在的分子机制。我们观察到 LPS 诱导的 J774A.1 细胞和胶原诱导的关节炎小鼠模型中 MIAT 表达升高，而 miR-30a-5p 的表达模式则相反。沉默 MIAT 导致炎症细胞因子 IL-1β 和 TNF-α 的表达增加。同时，MIAT 干扰显著抑制巨噬细胞自噬，表现为自噬相关标志物 LC3-II 和 Beclin-1 的表达减少，以及 LPS 诱导的 J774A.1 细胞中 p62 的水平升高。值得注意的是，MIAT 作为 ceRNA，与 miR-30a-5p 结合并对其表达产生负调控作用。SOCS1 是 miR-30a-5p 的靶标，受 MIAT 调节。机制上，抑制 miR-30a-5p 逆转了 MIAT 缺乏促进 LPS 诱导的炎症的影响，而 SOCS1 敲低则抵消了沉默 miR-30a-5p 诱导的细胞因子抑制作用。总之，本研究表明，lncRNA MIAT 通过刺激自噬来抑制 LPS 诱导的 J774A.1 巨噬细胞炎症，其机制是通过 miR-30a-5p/SOCS1 轴。这表明 MIAT 有望成为 RA 炎症的潜在治疗靶点。
