Tumor cell migration is affected by the aryl hydrocarbon receptor (AhR). However, the systematic molecular mechanisms underlying AhR-mediated migration of human neuroblastoma cells are not fully understood. To address this issue, we performed an integrative analysis of mRNA and microRNA (miR) expression profiles in human neuroblastoma SK-N-SH cells treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent agonist of AhR. The cell migration was increased in a time- and concentration- dependent manner, and was blocked by AhR antagonist (CH223191). A total of 4,377 genes were differentially expressed after 24-hour-treatment with 10^-10 M TCDD, of which the upregulated genes were significantly enriched in cell migration-related biological pathways. Thirty-four upregulated genes, of which 25 were targeted by 78 differentially expressed miRs, in the axon guidance pathway were experimentally confirmed, and the putative dioxin-responsive elements were present in the promoter regions of most genes (79 %) and miRs (82 %) in this pathway. Furthermore, two promigratory genes (CFL2 and NRP1) induced by TCDD was reversed by blockade of AhR. In conclusion, AhR-mediated mRNA-miR networks in the axon guidance pathway may represent a potential molecular mechanism of dioxin-induced directional migration of human neuroblastoma cells.

肿瘤细胞迁移受到芳烃受体（AhR）的影响。然而，AhR 介导的人神经母细胞瘤细胞迁移的系统分子机制尚不完全清楚。为了解决这个问题，我们对用 2,3,7,8-四氯二苯并-对二恶英 (TCDD)（一种有效激动剂）处理的人神经母细胞瘤 SK- N -SH 细胞中的 mRNA 和 microRNA (miR) 表达谱进行了综合分析AhR 的。细胞迁移以时间和浓度依赖性方式增加，并被 AhR 拮抗剂 (CH223191) 阻断。^{10 -10} M TCDD处理24小时后共有4,377个基因出现差异表达，其中上调基因显着富集于细胞迁移相关的生物学途径。实验证实了轴突引导通路中的 34 个上调基因，其中 25 个是 78 个差异表达 miR 的靶标，并且推定的二恶英反应元件存在于大多数基因 (79%) 和 miR (82%) 的启动子区域。 %) 在此途径中。此外，TCDD 诱导的两个前迁移基因（ CFL2和NRP1 ）通过阻断 AhR 被逆转。总之，轴突引导通路中 AhR 介导的 mRNA-miR 网络可能代表二恶英诱导人神经母细胞瘤细胞定向迁移的潜在分子机制。