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.
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.
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 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.
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.