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Summary: Preeclampsia (PE) is a leading cause of maternal and perinatal death. Accumulated evidence suggests that many long non‐coding RNAs (lncRNAs) are abnormally expressed in placentas from PE patients, and they may play functional roles in the development of PE. The present study aimed to investigate the functional role TUG1 in PE and explore the potential molecular mechanisms. Clinically, the expression of TUG1 in placental tissues from PE and normal controls was determined. In vitro, human trophoblast HTR‐8/SVneo and JAR cells were employed for loss or gain‐of‐function assays. Our results demonstrate that TUG1 was downregulated in PE placental tissues compared with normal controls. Moreover, downregulation of TUG1 inhibited the migration and invasion of trophoblast‐like cells. Bioinformatics analysis and functional assays showed that TUG1 interacted with miR‐204‐5p and negatively regulated the expression and function of miR‐204‐5p in trophoblast cells. Furthermore, TUG1‐mediated migration and invasion of trophoblast cells was regulated by miR‐204‐5p. Together, our results suggested that TUG1 regulates trophoblast migration and invasion partly through sponging miR‐204‐5p, and the TUG1/miR‐204‐5p axis could be a potential therapeutic target for the treatment of PE. [ABSTRACT FROM AUTHOR]

Insufficient trophoblast invasion often occurs in patients experiencing preeclampsia. The 67-kDa laminin receptor ( LR1) is a multifunctional protein that binds to laminin and interacts with the extracellular matrix. We recently demonstrated that LR1 is implicated in trophoblast migration and invasion. However, whether LR1 is involved in hypoxia-mediated trophoblastic invasion remains unclear and requires further investigation. This study demonstrates that two trophoblast-like cell lines ( JEG3 and BeWo cells) cultured at 3% oxygen exerted enhanced migratory and invasive capabilities as compared with their counterparts exposed to 20% oxygen. LR1 expression was increased in hypoxic JEG3 cells but decreased after transfection with hypoxia-inducible factor 1 alpha ( HIF-1 α) specific si RNA. Moreover, sh RNA targeting LR1 m RNA significantly inhibited hypoxia-induced increase in matrix metalloproteinase ( MMP)-9 activity in JEG3 cells. Forced overexpression of LR1 augmented JEG3 cell migration and invasion, and enhanced MMP-9 expression and activity. Additionally, the blockade of the MMP-9 effect with its neutralizing antibody reduced LR1 elevation-promoted trophoblastic invasion. In summary, this study demonstrates that LR1 contributes to hypoxia-induced migration and invasion of trophoblast cells at least partly by mediating MMP-9 in vitro. [ABSTRACT FROM AUTHOR]