PFOS-induced placental cell growth inhibition is partially mediated by lncRNA H19 through interacting with miR-19a and miR-19b
PFOS-induced placental cell growth inhibition is partially mediated by lncRNA H19 through interacting with miR-19a and miR-19b
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PFOS 诱导的胎盘细胞生长抑制部分由 lncRNA H19 通过与 miR-19a 和 miR-19b 相互作用介导
DOI：
10.1016/j.chemosphere.2020.127640
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发表时间：
2020-12-01
期刊：
影响因子：
8.8
通讯作者：
Yu, Hong-Min
中科院分区：
文献类型：
--
作者：
Li, Jing;Quan, Xiao-jie;Yu, Hong-Min
全氟辛烷磺酸是一种持久性环境污染物，与出生体重下降有关。长链非编码RNA（lncRNA）H19的表达异常与妊娠并发症如宫内生长迟缓（IUGR）、先兆子痫（PE）等密切相关，然而H19在PFOS对胎盘的有害作用中的表达和功能尚不清楚。在这里，我们探讨了H19在全氟辛烷磺酸诱导的胎盘毒性中的作用。结果表明，全氟辛烷磺酸导致人类HTR-8/SVneo细胞生长减缓。在接触全氟辛烷磺酸的小鼠胎盘组织和HTR-8/SVneo细胞中，H19的表达增加，而miR-19-a和miR-19 b的表达减少。在妊娠期接触高剂量全氟辛烷磺酸的小鼠的胎盘中，观察到H19启动子出现显著的低甲基化。证实H19与靶向SMAD 4的miR-19 a和miR-19 b结合。此外，H19似乎通过上调miR-19 a和miR-19 b，部分改善了暴露于全氟辛烷磺酸的HTR-8/SVneo细胞的细胞生长。综上所述，我们的研究结果表明，H19/ miR-19 a和miR-19 b/SMAD 4轴在PFOS诱导的胎盘细胞毒性中发挥重要作用。(C)2020爱思唯尔有限公司保留所有权利。
Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has been associated with decreased birth weight. The dysregulation of long non-coding RNA (lncRNA) H19 has been implicated in pregnancy complications such as intra-uterine growth retardation (IUGR), preeclampsia (PE), however, the expression and function of H19 in PFOS-exerted detrimental effects in the placenta remains to be unveiled. Here, we explored the role of H19 in PFOS-induced placental toxicity. Results showed that PFOS caused decreased cell growth in human HTR-8/SVneo cells. Expression of H19 was increased, while miR19-a and miR-19b expression were decreased in mice placenta tissues and in HTR-8/SVneo cells exposed to PFOS. A significant hypomethylation was observed at the H19 promoter in the placentas of mice that were gestational exposed to high dose of PFOS. H19 was confirmed to bind with miR-19a and miR-19b, targeting SMAD4. Furthermore, H19 appeared to partially improve the cell growth of HTR-8/SVneo cells exposed to PFOS via upregulation of miR-19a and miR-19b. In summary, our findings revealed that H19/ miR-19a and miR-19b/SMAD4 axis exerted important functions in PFOS-induced placenta cell toxicity. (C) 2020 Elsevier Ltd. All rights reserved.