LncRNA MALAT1 affects the migration and invasion of trophoblast cells by regulating FOS expression in early-onset preeclampsia
LncRNA MALAT1 affects the migration and invasion of trophoblast cells by regulating FOS expression in early-onset preeclampsia
复制标题
LncRNA MALAT1通过调节早发子痫前期FOS表达影响滋养层细胞迁移和侵袭
DOI：
10.1016/j.preghy.2020.05.001
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发表时间：
2020-07-01
影响因子：
2.2
通讯作者：
Sun, Lizhou
中科院分区：
文献类型：
--
作者：
Li, Qin;Wang, Tianjun;Sun, Lizhou
背景资料：先兆子痫（PE），特别是早发性PE（ePE），引起母体和胎儿并发症，并且仍然是现代社会的主要健康问题。异常的子宫螺旋动脉重塑通过不良的胎盘形成导致ePE。在这项研究中，我们研究了长链非编码RNA（lncRNA）MALAT 1在ePE发病mechanism.Methods的作用：总RNA提取自40对胎盘ePE组织和对照组。通过qRT-PCR定量RNA水平，并通过蛋白质印迹和免疫组织化学（IHC）分析测定蛋白质表达。在HTR-8/SVneo细胞和THP细胞中评估MALAT 1对滋养层迁移和侵袭的影响。通过RNA-seq鉴定FOS为MALAT 1的下游功能基因。结果：MALAT 1在ePE胎盘组织中表达水平较低，其沉默（-/-）抑制滋养层细胞的侵袭和迁移。MALAT 1-/-也降低了N-钙粘蛋白和波形蛋白的表达，但增加了E-钙粘蛋白的表达。RNA-seq分析和随后的RIP测定表明，MALAT 1通过HuR结合改善FOS。FOS过表达同样增强滋养层细胞迁移和侵袭。免疫组化结果显示，ePE组胎盘组织中E-cadherin表达上调，FOS、N-cadherin和vimentin表达下调。结论：MALAT 1通过FOS诱导的上皮间质转化（EMT）促进滋养细胞迁移和侵袭。这突出了MALAT 1在ePE发病机制中螺旋动脉重塑受损中的新作用。
Background: Preeclampsia (PE), particularly early-onset PE (ePE), causes maternal and fetal complications and remains a major health problem in modern society. Aberrant uterine spiral artery remodeling leads to ePE through poor placentation. In this study, we investigated the role of the long non-coding RNA (lncRNA) MALAT1 in ePE pathogenesis.Methods: Total RNA was extracted from 40 paired placental ePE tissues and control groups. RNA levels were quantified by qRT-PCR and protein expression was determined by western blot and immunohistochemistry (IHC) analysis. The effects of MALAT1 on trophoblast migration and invasion were evaluated in HTR-8/SVneo and JAR cells. FOS was identified as a downstream functional gene of MALAT1 by RNA-seq. RNA binding protein immunoprecipitations (RIPs) were performed to reveal the cellular targets of MALAT1.Results: MALAT1 was poorly expressed in ePE placentas and its silencing (-/-) inhibited trophoblast invasion and migration. MALAT1 -/- also decreased N-cadherin and vimentin expression, but increased E-cadherin expression. RNA-seq analysis and subsequent RIP assays showed that MALAT1 improved FOS through Hu-antigen R (HuR) binding. FOS overexpression similarly enhanced trophoblast migration and invasion. IHC staining showed that E-cadherin was upregulated in placenta tissue from ePE groups, whilst FOS, N-cadherin, and vimentin were downregulated.Conclusion: MALAT1 promotes trophoblast migration and invasion through FOS-induced epithelial mesenchymal transition (EMT). This highlights new roles for MALAT1 in the impairment of spiral artery remodeling in ePE pathogenesis.