Li Qin, Wang Tianjun, Huang Shiyun, Zuo Qing, Jiang Ziyan, Yang Nana, Sun Lizhou
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Pregnancy Hypertens. 2020 Jul;21:50-57. doi: 10.1016/j.preghy.2020.05.001. Epub 2020 May 6.
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.
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 blotand 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.
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.
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.
子痫前期（PE），尤其是早发型子痫前期（ePE），会导致母婴并发症，仍是现代社会中的一个主要健康问题。子宫螺旋动脉重塑异常通过胎盘形成不良导致ePE。在本研究中，我们调查了长链非编码RNA（lncRNA）MALAT1在ePE发病机制中的作用。
从40对胎盘ePE组织和对照组中提取总RNA。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）分析确定蛋白质表达。在HTR-8/SVneo和JAR细胞中评估MALAT1对滋养细胞迁移和侵袭的影响。通过RNA测序将FOS鉴定为MALAT1的下游功能基因。进行RNA结合蛋白免疫沉淀（RIP）以揭示MALAT1的细胞靶点。
MALAT1在ePE胎盘中表达不佳，其沉默（-/-）抑制滋养细胞侵袭和迁移。MALAT1 -/-还降低了N-钙黏蛋白和波形蛋白的表达，但增加了E-钙黏蛋白的表达。RNA测序分析和随后的RIP分析表明，MALAT1通过与Hu抗原R（HuR）结合来上调FOS。FOS过表达同样增强了滋养细胞的迁移和侵袭。IHC染色显示，ePE组胎盘组织中E-钙黏蛋白上调，而FOS、N-钙黏蛋白和波形蛋白下调。
MALAT1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MALAT1在ePE发病机制中螺旋动脉重塑受损方面的新作用。
