Systematic identification of molecular mechanisms for aryl hydrocarbon receptor mediated neuroblastoma cell migration

Tuan Xu; Yali Luo; Heidi Qunhui Xie; Yingjie Xia; Yunping Li; Yangsheng Chen; Zhiling Guo; Li Xu; Bin Zhao

doi:10.1016/j.envint.2022.107461

Systematic identification of molecular mechanisms for aryl hydrocarbon receptor mediated neuroblastoma cell migration

Environ Int. 2022 Oct:168:107461. doi: 10.1016/j.envint.2022.107461. Epub 2022 Aug 10.

Authors

Tuan Xu¹, Yali Luo¹, Heidi Qunhui Xie², Yingjie Xia¹, Yunping Li¹, Yangsheng Chen¹, Zhiling Guo¹, Li Xu¹, Bin Zhao³

Affiliations

¹ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
² State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: qhxie@rcees.ac.cn.
³ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: binzhao@rcees.ac.cn.

PMID: 35981476
DOI: 10.1016/j.envint.2022.107461

Abstract

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.

Keywords: Aryl hydrocarbon receptor; Axon guidance pathway; Cell migration; Dioxin; Multi-omics; microRNA.