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Accumulating evidence has indicated that long noncoding RNAs are aberrantly expressed in PE, whereas detailed mechanisms are unknown. In the present study, we showed that lncRNA Taurine upregulated 1 (TUG1) were downregulated in preeclamptic placenta and in HTR8\/SVneo cells under hypoxic conditions, together with reduced enhancer of zeste homolog2 (EZH2) and embryonic ectoderm development (EED) expression, major components of polycomb repressive complex 2 (PRC2), as well as activation of Nodal\/ALK7 signalling pathway. Mechanistically, we found that TUG1 bound to PRC2 (EZH2\/EED) in HTR8\/SVneo cells and weakened TUG1\/PRC2 interplay was correlated with upregulation of Nodal expression via decreasing H3K27me3 mark at the promoter region of Nodal gene under hypoxic conditions. And activation of Nodal signalling prohibited trophoblast invasion via reducing MMP2 levels. Overexpression of TUG1 or EZH2 significantly attenuated hypoxia\u2010induced reduction of trophoblastic invasiveness via negative modulating Nodal\/ALK7 signalling and rescuing expression of its downstream target MMP2. These investigations might provide some evidence for novel mechanisms responsible for inadequate trophoblastic invasion and might shed some light on identifying future therapeutic targets for PE.<\/jats:p>","DOI":"10.1111\/jcmm.17450","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:39:07Z","timestamp":1655872747000},"page":"4087-4100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hypoxia induced\u2010disruption of lncRNA TUG1\/PRC2 interaction impairs human trophoblast invasion through epigenetically activating Nodal\/ALK7 signalling"],"prefix":"10.1111","volume":"26","author":[{"given":"Mengsi","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shandong Provincial Hospital, Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Department of Nephrology Shandong Provincial Hospital Affiliated to Shandong First Medical 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