LINC01686 affects LPS‐induced cytokine expression via the miR‐18a‐5p/A20/STAT1 axis in THP‐1 cells

Abstract

AbstractBackground and ObjectiveLong 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.MethodTHP‐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.ResultsLINC01686 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.ConclusionThis 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.