Departments of Medicine, McGill University, Montreal, Quebec, Canada.
Research Institute of the McGill University Health Centre (RI-MUHC), Meakins-Christie Laboratories, Montreal, QC, Canada.
Sci Rep. 2017 Jan 12;7:40539. doi: 10.1038/srep40539.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr and Ahr mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array. There was a dramatic regulation of lung miRNA by the AhR in the absence of exogenous ligand. In response to cigarette smoke, there were more up-regulated miRNA in Ahr mice compared to Ahr mice, including the cancer-associated miRNA miR-96. There was no significant change in the expression of the AhR regulated proteins HuR and cyclooxygenase-2 (COX-2). There were significant increases in the anti-oxidant gene sulfiredoxin 1 (Srxn1) and FOXO3a- predicted targets of miR-96. Collectively, these data support a prominent role for the AhR in regulating lung miRNA expression. Further studies to elucidate a role for these miRNA may further uncover novel biological function for the AhR in respiratory health and disease.
芳香烃受体 (AhR) 是一种配体激活的转录因子，历史上因其对二恶英等人为污染物的毒性反应而闻名。最近，AhR 已成为一种通过可能涉及 microRNA 调节的机制来抑制香烟烟雾引起的炎症、氧化应激和细胞凋亡的因子。然而，对于 AhR 如何调节吸入性毒物在肺部的 microRNA 表达知之甚少。因此，我们使 Ahr 和 Ahr 小鼠暴露于香烟烟雾中 4 周，并通过 PCR 阵列评估肺 microRNA 表达。在没有外源性配体的情况下，AhR 对肺 microRNA 有明显的调节作用。与 Ahr 小鼠相比，Ahr 小鼠对香烟烟雾的反应中有更多上调的 microRNA，包括与癌症相关的 microRNA miR-96。AhR 调节蛋白 HuR 和环氧化酶-2 (COX-2) 的表达没有明显变化。抗氧化基因 sulfiredoxin 1 (Srxn1) 和 FOXO3a 的表达显著增加——miR-96 的预测靶点。总的来说，这些数据支持 AhR 在调节肺 microRNA 表达中的重要作用。进一步研究这些 microRNA 的作用可能会进一步揭示 AhR 在呼吸健康和疾病中的新生物学功能。
