Up-regulation of microRNA-34a mediates ethanol-induced impairment of neural crest cell migration in vitro and in zebrafish embryos through modulating epithelial-mesenchymal transition by targeting Snail1.
Up-regulation of microRNA-34a mediates ethanol-induced impairment of neural crest cell migration in vitro and in zebrafish embryos through modulating epithelial-mesenchymal transition by targeting Snail1.
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DOI：
10.1016/j.toxlet.2022.01.004
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发表时间：
2022-04-01
影响因子：
3.5
通讯作者：
Chen, Shao-yu
中科院分区：
文献类型：
--
作者：
Fan, Huadong;Li, Yihong;Yuan, Fuqiang;Lu, Lanhai;Liu, Jie;Feng, Wenke;Zhang, Huang-Ge;Chen, Shao-yu
产前乙醇暴露可损害神经嵴细胞（NCC）的发育，包括NCC的存活、分化和迁移，导致胎儿酒精谱系障碍（FASD）的颅面畸形。上皮-间质转化（Epithelial-mesenchymal transition， EMT）在调控细胞迁移中起重要作用。本研究的目的是确定乙醇暴露是否可以通过抑制EMT来抑制NCC的迁移，以及microRNA-34a （miR-34a）是否参与了乙醇诱导的NCC的EMT损伤。我们发现，暴露于100 mM乙醇显著抑制NCCs的迁移。qRT-PCR和Western Blot分析显示，乙醇暴露显著降低了Snail1的mRNA和蛋白表达，Snail1是一个在EMT调控中起关键作用的关键转录因子。乙醇暴露也显著增加了Snail1靶基因E-cadherin1的mRNA表达，抑制了ncc的EMT。我们还发现，暴露于乙醇显著提高了ncc中靶向Snail1的miR-34a的表达。此外，miR-34a的下调阻止了乙醇诱导的Snail1的抑制，并减少了乙醇诱导的ncc中Snail1靶基因E-cadherin1的上调。在体外和斑马鱼胚胎中，抑制miR-34a可以恢复EMT，并阻止乙醇诱导的NCC迁移抑制。这些结果表明，乙醇诱导的miR-34a上调通过靶向Snail1抑制EMT，有助于NCC迁移的损害。
Prenatal ethanol exposure can impair neural crest cell (NCC) development, including NCC survival, differentiation and migration, contributing to the craniofacial dysmorphology in Fetal Alcohol Spectrum Disorders (FASD). Epithelial-mesenchymal transition (EMT) plays an important role in regulating the migration of NCCs. The objective of this study is to determine whether ethanol exposure can suppress NCC migration through inhibiting EMT and whether microRNA-34a (miR-34a) is involved in the ethanol-induced impairment of EMT in NCCs. We found that exposure to 100 mM ethanol significantly inhibited the migration of NCCs. qRT-PCR and Western Blot analysis revealed that exposure to ethanol robustly reduced the mRNA and protein expression of Snail1, a critical transcriptional factor that has a pivotal role in the regulation of EMT. Ethanol exposure also significantly increased the mRNA expression of the Snail1 target gene E-cadherin1 and inhibited EMT in NCCs. We also found that exposure to ethanol significantly elevated the expression of miR-34a that targets Snail1 in NCCs. In addition, down-regulation of miR-34a prevented ethanol-induced repression of Snail1 and diminished ethanol-induced upregulation of Snail1 target gene E-cadherin1 in NCCs. Inhibition of miR-34a restored EMT and prevented ethanol-induced inhibition of NCC migration in vitro and in zebrafish embryos in vivo. These results demonstrate that ethanol-induced upregulation of miR-34a contributes to the impairment of NCC migration through suppressing EMT by targeting Snail1.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
DOI：
10.1016/j.reprotox.2013.08.003
发表时间：
2013-12
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Chen X;Liu J;Chen SY
通讯作者：
Chen SY
影响因子：
7.3
作者：
Chen, X.;Liu, J.;Chen, S-Y
通讯作者：
Chen, S-Y
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.