Dioxin induces expression of hsa-miR-146b-5p in human neuroblastoma cells


Tuan Xu , Heidi Q. Xie , Yunping Li , Yingjie Xia , Rui Sha , Lingyun Wang , Yangsheng Chen , Li Xu , Bin Zhao

DOI:10.1016/j.jes.2017.06.038

Received February 14, 2017,Revised June 16, 2017, Accepted June 30, 2017, Available online July 11, 2017

Volume 30,2018,Pages 260-267

Dioxin can cause a series of neural toxicological effects. MicroRNAs (miRs) play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-miR-146b-5p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-miR-146b-5p. We found that the hsa-miR-146b-5p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-miR-146b-5p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-miR-146b-5p significantly suppressed acetylcholinesterase (AChE) activity and targeted the 3′-untranslated region of the AChE T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-miR-146b-5p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which AChE may serve as a responsive gene for mediating the effect.

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