3.2.1. LncRNAs in Preeclampsia

Long non-coding RNAs are RNA molecules longer than 200 nucleotides which are involved in regulation of cell function through a wide range of mechanisms. lncRNAs are expressed in the nucleus

as single stranded RNA molecules, which can either function in their native form or undergo maturation through the addition of a <sup>5</sup>cap and polyA tail; however, they are never translated into a protein product [229]. They regulate cell function by a wide range of mechanisms: alteration of the stability of target mRNAs, direct recruitment of chromatin modification enzymes, segregation of transcription factors through specific binding sites contained within the lncRNA sequence, warehousing miRNA as 'miRNA sponges', a function shared with circular RNAs [230]. For a complete overview please see Reference [231].

Transcriptomic analyses of placenta and decidua total RNAs allowed identifying di fferentially expressed lncRNAs between PE and control patients, often with a di fference between EOPE and LOPE [228,232,233]. Most of these lncRNAs had been previously identified in the field of cancer research, often associated with cell proliferation, migration and invasion [234]. As mentioned above, given the parallels between the features of cancer cells and the trophoblasts during placentation such as fast proliferation of the trophoblast, migration and invasion of the maternal tissues, immunotolerance [235–238], this did not come as a surprise and has prompted extensive in vitro research to elucidate the roles of these lncRNAs in trophoblast physiology.

In the present review, we will focus on a few lncRNAs that have been well characterized: MALAT-1, MEG3, RNA-ATB. Finally, we will give a brief overview on how in PE some lncRNAs regulate gene expression by altering chromatin methylation state of their target genes, through direct recruitment of histone methyltransferases, bringing as examples PVT1, TUG1 and DIAPH2-AS1. H19 was discussed above for its important role in placental development and miRNA encoding lncRNA.
