Systematic identification of molecular mechanisms for aryl hydrocarbon receptor mediated neuroblastoma cell migration
Autor: | Tuan Xu, Yali Luo, Heidi Qunhui Xie, Yingjie Xia, Yunping Li, Yangsheng Chen, Zhiling Guo, Li Xu, Bin Zhao |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: | |
Zdroj: | Environment International, Vol 168, Iss , Pp 107461- (2022) |
Druh dokumentu: | article |
ISSN: | 0160-4120 |
DOI: | 10.1016/j.envint.2022.107461 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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