Rapid Fire & Poster Presentation 40th Annual Lorne Genome Conference 2019

lncRNA expression and function in the human placenta (#205)

Erica P Langley 1 2 , Benjamin T Mayne 1 2 , Dale McAninch 1 2 , Tanja Jankovic-Karasoulos 1 2 , Shalem Y Leemaqz 1 2 , Prabha Andraweera 1 2 , Dylan McCullough 1 2 , Jimmy Breen 1 3 , Claire Roberts 1 2 , Tina Bianco-Miotto 1 4
  1. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
  2. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
  3. Bioinformatics Hub, School of Biological Sciences, University of Adelaide, Adelaide, SA
  4. Waite Research Institute, School of Agriculture, Food and Wine, University of Adelaide, Adelaide, SA

The placenta is critical for pregnancy success and yet we do not have a complete molecular understanding of how it develops. Importantly, the placenta shares cellular and molecular similarities with cancer but its tumour-like growth and invasive behaviour are tightly controlled. Defects in placental development contribute to pregnancy complications such as preeclampsia. Delineating the key molecular regulators of placental trophoblast cell differentiation and function would be beneficial in understanding pregnancy complications and provide insight into the pathways involved in controlling processes that are the hallmark of cancer growth. Long non-coding RNAs (lncRNAs) are expressed in a cell specific manner and are aberrantly expressed in cancers, contributing to tumour progression and metastasis. Studies have shown that lncRNAs are also dysregulated in pregnancy complications but the role of lncRNAs in normal placental development is largely unknown. This study investigated the expression and function of four lncRNAs which have previously been shown to have important roles in tumorigenesis and one lncRNA identified from RNA-sequencing data as a potentially novel and placenta specific lncRNA. lncRNA expression was examined in placenta tissue by qPCR from first trimester (n=9), second trimester (n=10), uncomplicated term (n=9) and preeclamptic (n=6) pregnancies. LINC00284 was downregulated in first (p=0.0014) and second (p=0.011) trimester compared to term. DANCR was downregulated in term placenta compared to first trimester (p<0.0001). DANCR, SNHG1 and lncRNA-LET were upregulated in placentas from pregnancies affected by preeclampsia (p<0.05). In situ hybridisation localised DANCR to trophoblast cells in first trimester tissue. Knockdown of DANCR decreased endothelial-like tube formation and length (p<0.0001) without affecting viability in an extravillous trophoblast cell line. We have shown that lncRNAs, previously identified as having an important role in tumorigenesis, may also be important in placental trophoblast cell function warranting further investigation into their role in trophoblast differentiation and their disruption in pregnancy complications.