LINC01686 通过 miR-18a-5p/A20/STAT1 轴影响 LPS 诱导的 THP-1 细胞细胞因子表达。

BACKGROUND AND OBJECTIVE: Long noncoding RNAs (lncRNAs) are crucial in regulating various physiological and pathological processes, including immune responses. LINC01686 is a lncRNA with previously uncharacterized functions in immune regulation. This study aims to investigate the function of LINC01686 in lipopolysaccharide (LPS)-induced inflammatory responses in the human monocytic leukemia cell line THP-1 and its potential regulatory mechanisms involving miR-18a-5p and the anti-inflammatory protein A20. METHOD: THP-1 cells were stimulated with LPS to induce inflammatory responses, followed by analysis of LINC01686 expression levels. The role of LINC01686 in regulating the expression of interleukin (IL)-6, IL-8, A20, and signal transducer and activator of transcription 1 (STAT1) was examined using small interfering RNA-mediated knockdown. Additionally, the involvement of miR-18a-5p in LINC01686-mediated regulatory pathways was assessed by transfection with decoy RNAs mimicking the miR-18a-5p binding sites of LINC01686 or A20 messenger RNA. RESULTS: LINC01686 expression was upregulated in THP-1 cells following LPS stimulation. Suppression of LINC01686 enhanced LPS-induced expression of IL-6 and IL-8, mediated through increased production of reactive oxygen species. Moreover, LINC01686 knockdown upregulated the expression and activation of IκB-ζ, STAT1, and downregulated A20 expression. Transfection with decoy RNAs reversed the effects of LINC01686 suppression on A20, STAT1, IL-6, and IL-8 expression, highlighting the role of LINC01686 in sponging miR-18a-5p and regulating A20 expression. CONCLUSION: This study provides the first evidence that LINC01686 plays a critical role in modulating LPS-induced inflammatory responses in THP-1 cells by sponging miR-18a-5p, thereby regulating the expression and activation of A20 and STAT1. These findings shed light on the complex regulatory mechanisms involving lncRNAs in immune responses and offer potential therapeutic targets for inflammatory diseases.

背景与目的：长链非编码 RNA（lncRNA）在调节各种生理和病理过程中起着关键作用，包括免疫反应。LINC01686 是一种在免疫调节中功能尚未明确的 lncRNA。本研究旨在探讨 LINC01686 在脂多糖（LPS）诱导的人单核白血病细胞系 THP-1 炎症反应中的功能及其潜在的调控机制，涉及 miR-18a-5p 和抗炎蛋白 A20。

方法：用 LPS 刺激 THP-1 细胞诱导炎症反应，然后分析 LINC01686 的表达水平。用小干扰 RNA 介导的敲低研究 LINC01686 调节白细胞介素（IL）-6、IL-8、A20 和信号转导和转录激活因子 1（STAT1）表达的作用。此外，通过转染 LINC01686 或 A20 信使 RNA 的 miR-18a-5p 结合位点的模拟物 decoy RNA，评估 miR-18a-5p 在 LINC01686 介导的调控途径中的作用。

结果：LPS 刺激后，THP-1 细胞中 LINC01686 的表达上调。抑制 LINC01686 增强了 LPS 诱导的 IL-6 和 IL-8 的表达，这是通过增加活性氧的产生介导的。此外，LINC01686 敲低上调了 IκB-ζ、STAT1 的表达和激活，并下调了 A20 的表达。转染 decoy RNA 逆转了 LINC01686 抑制对 A20、STAT1、IL-6 和 IL-8 表达的影响，突出了 LINC01686 在海绵 miR-18a-5p 并调节 A20 表达中的作用。

结论：本研究首次证明，LINC01686 通过海绵 miR-18a-5p 在 LPS 诱导的 THP-1 细胞炎症反应中发挥关键作用，从而调节 A20 和 STAT1 的表达和激活。这些发现揭示了 lncRNA 在免疫反应中涉及的复杂调控机制，并为炎症性疾病提供了潜在的治疗靶点。