Clinical Medicine College, Weifang Medical University, Weifang, China.
Department of Gastrointestinal and Anal Diseases Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, China.
Front Immunol. 2019 Sep 18;10:2218. doi: 10.3389/fimmu.2019.02218. eCollection 2019.
Accumulating studies have suggested that long non-coding RNAs (lncRNAs) have drawn more and more attention in rheumatoid arthritis (RA), which can function as competitive endogenous RNAs (ceRNAs) in inflammation and immune disorders. Previously, we have found that lncRNA HIX003209 is differentially expressed in RA. However, the precise mechanism of lncRNA HIX003209 in RA is still vague. We aim to elucidate the role and its targeted microRNA of lncRNA HIX003209 in RA as ceRNA. Significantly increased expression of lncRNA HIX003209 was observed in the peripheral blood mononuclear cells (PBMCs) from RA cases. It was positively associated with TLR2 and TLR4 in RA. Besides, peptidoglycan (PGN) and lipopolysaccharide (LPS) could enhance the expression of lncRNA HIX003209, which reversely promoted the proliferation and activation of macrophages through IκBα/NF-κB signaling pathway. Moreover, HIX003209 was involved in TLR4-mediated inflammation via targeting miR-6089 in macrophages. LncRNA HIX003209 functions as a ceRNA and exaggerates inflammation by sponging miR-6089 through TLR4/NF-κB pathway in macrophages, which offers promising therapeutic strategies for RA.
越来越多的研究表明，长非编码 RNA（lncRNA）在类风湿关节炎（RA）中引起了越来越多的关注，它们可以作为炎症和免疫紊乱中的竞争性内源性 RNA（ceRNA）发挥作用。此前，我们发现 lncRNA HIX003209 在 RA 中表达差异。然而，lncRNA HIX003209 在 RA 中的精确机制仍不清楚。我们旨在阐明 lncRNA HIX003209 在 RA 中作为 ceRNA 的作用及其靶向 microRNA。在 RA 患者的外周血单核细胞（PBMCs）中观察到 lncRNA HIX003209 的表达显著增加。它与 RA 中的 TLR2 和 TLR4 呈正相关。此外，肽聚糖（PGN）和脂多糖（LPS）可以增强 lncRNA HIX003209 的表达，通过 IκBα/NF-κB 信号通路反向促进巨噬细胞的增殖和激活。此外，HIX003209 通过靶向巨噬细胞中的 miR-6089 参与 TLR4 介导的炎症。lncRNA HIX003209 通过 TLR4/NF-κB 通路作为 ceRNA 发挥作用，并通过 TLR4/NF-κB 通路吸收 miR-6089 来夸大炎症，为 RA 提供了有前途的治疗策略。
