Long noncoding RNAs (lncRNAs) are central regulators of the inflammatory response and play an important role in inflammatory diseases. PINT has been reported to be involved in embryonic development and tumorigenesis. However, the potential functions of PINT in the innate immune system are largely unknown. Here, we revealed the transcriptional regulation of inflammatory genes by PINT, whose expression is primarily dependent on the NF-κB signaling pathway in human and mouse macrophage and intestinal epithelial cell lines. Functionally, PINT selectively regulates the expression of TNF-α in basal and LPS-stimulated cells. Mechanistically, PINT acts as a modular scaffold of p65 and EZH2 to coordinate their localization and specify their binding to the target genes. Further, a high expression level of PINT was detected in intestinal mucosal tissues from patients with ulcerative colitis (UC). Together, these findings demonstrate that PINT acts as an activator of inflammatory responses, highlighting the importance of this lncRNA as a potential therapeutic target in infectious diseases and inflammatory diseases.

中文翻译：

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NF-κB 响应长非编码 RNA，PINT，通过支架 p65 和 EZH2 调节 TNF-α 基因转录

长链非编码 RNA (lncRNA) 是炎症反应的中心调节因子，在炎症性疾病中发挥重要作用。据报道，PINT 参与胚胎发育和肿瘤发生。然而，PINT 在先天免疫系统中的潜在功能在很大程度上是未知的。在这里，我们揭示了 PINT 对炎症基因的转录调控，其表达主要依赖于人和小鼠巨噬细胞和肠上皮细胞系中的 NF-κB 信号通路。在功能上，PINT 选择性地调节基底细胞和 LPS 刺激细胞中 TNF-α 的表达。从机制上讲，PINT 充当 p65 和 EZH2 的模块化支架，以协调它们的定位并指定它们与靶基因的结合。更远，在溃疡性结肠炎 (UC) 患者的肠黏膜组织中检测到 PINT 的高表达水平。总之，这些发现表明 PINT 作为炎症反应的激活剂，突出了该 lncRNA 作为传染病和炎症疾病潜在治疗靶点的重要性。