MicroRNA-135a Protects Against Ethanol-Induced Apoptosis in Neural Crest Cells and Craniofacial Defects in Zebrafish by Modulating the Siah1/p38/p53 Pathway.
MicroRNA-135a Protects Against Ethanol-Induced Apoptosis in Neural Crest Cells and Craniofacial Defects in Zebrafish by Modulating the Siah1/p38/p53 Pathway.
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DOI：
10.3389/fcell.2020.583959
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发表时间：
2020
影响因子：
5.5
通讯作者：
Chen SY
中科院分区：
文献类型：
--
作者：
Yuan F;Yun Y;Fan H;Li Y;Lu L;Liu J;Feng W;Chen SY
MicroRNA (miRNA) 是小型非编码 RNA，通过调节基因表达参与多种生物过程，包括细胞凋亡。本研究旨在检验以下假设：乙醇诱导的 miR-135a 下调通过上调 Siah1 并激活 p38 丝裂原激活蛋白激酶 (MAPK)/p53 通路，从而导致乙醇诱导的神经嵴细胞 (NCC) 细胞凋亡。我们发现乙醇处理导致 NCC 和斑马鱼胚胎中 miR-135a 表达显着下降。乙醇诱导的 miR-135a 下调导致 Siah1 上调和 p38 MAPK/p53 通路激活，并增加 NCC 和斑马鱼胚胎的细胞凋亡。乙醇暴露还会导致生长迟缓和发育缺陷，这是斑马鱼胎儿酒精谱系障碍（FASD）的特征。 miRNA-135a 的过表达显着降低了乙醇诱导的 Siah1 上调和 p38 MAPK/p53 通路的激活，并减少了 NCC 和斑马鱼胚胎中乙醇诱导的细胞凋亡。此外，显微注射 miRNA-135a 模拟物可显着减少乙醇诱导的斑马鱼幼虫生长迟缓和颅面缺陷。这些结果表明，乙醇诱导的 miR-135a 下调通过上调 Siah1 和激活 p38 MAPK/p53 通路，有助于乙醇诱导的 NCC 细胞凋亡，并且 miRNA-135a 的过表达可以防止乙醇诱导的 NCC 细胞凋亡和 FASD 斑马鱼模型中的颅面缺陷。
MicroRNAs (miRNAs) are small non-coding RNAs that are involved in various biological processes, including apoptosis, by regulating gene expression. This study was designed to test the hypothesis that ethanol-induced downregulation of miR-135a contributes to ethanol-induced apoptosis in neural crest cells (NCCs) by upregulating Siah1 and activating the p38 mitogen-activated protein kinase (MAPK)/p53 pathway. We found that treatment with ethanol resulted in a significant decrease in miR-135a expression in both NCCs and zebrafish embryos. Ethanol-induced downregulation of miR-135a resulted in the upregulation of Siah1 and the activation of the p38 MAPK/p53 pathway and increased apoptosis in NCCs and zebrafish embryos. Ethanol exposure also resulted in growth retardation and developmental defects that are characteristic of fetal alcohol spectrum disorders (FASD) in zebrafish. Overexpression of miRNA-135a significantly reduced ethanol-induced upregulation of Siah1 and the activation of the p38 MAPK/p53 pathway and decreased ethanol-induced apoptosis in NCCs and zebrafish embryos. In addition, ethanol-induced growth retardation and craniofacial defects in zebrafish larvae were dramatically diminished by the microinjection of miRNA-135a mimics. These results demonstrated that ethanol-induced downregulation of miR-135a contributes to ethanol-induced apoptosis in NCCs by upregulating Siah1 and activating the p38 MAPK/p53 pathway and that the overexpression of miRNA-135a can protect against ethanol-induced apoptosis in NCCs and craniofacial defects in a zebrafish model of FASD.
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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：
2.9
作者：
Bilotta, J;Barnett, JA;Saszik, S
通讯作者：
Saszik, S
影响因子：
8
作者：
Kroiss, A.;Vincent, S.;Allioli, N.
通讯作者：
Allioli, N.
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：
8
作者：
Hong, F;Kim, WH;Gao, B
通讯作者：
Gao, B