TY - JOUR
T1 - Systematic identification of molecular mechanisms for aryl hydrocarbon receptor mediated neuroblastoma cell migration
AU - Xu, Tuan
AU - Luo, Yali
AU - Xie, Heidi Qunhui
AU - Xia, Yingjie
AU - Li, Yunping
AU - Chen, Yangsheng
AU - Guo, Zhiling
AU - Xu, Li
AU - Zhao, Bin
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - Aryl hydrocarbon receptor
KW - Axon guidance pathway
KW - Cell migration
KW - Dioxin
KW - Multi-omics
KW - microRNA
UR - http://www.scopus.com/inward/record.url?scp=85135948246&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2022.107461
DO - 10.1016/j.envint.2022.107461
M3 - Article
SN - 0160-4120
VL - 168
JO - Environment International
JF - Environment International
M1 - 107461
ER -