title: miR455 is linked to hypoxia signaling and is deregulated in preeclampsia.
abstract: Preeclampsia is a severe pregnancy-related disorder and a leading cause of maternal and fetal mortality worldwide. Early identification of patients with an increased risk for preeclampsia is thus one of the most important goals in obstetrics. Here we identify two related human microRNAs as potential biomarkers to detect at-risk pregnancies. We demonstrate that miR455-3P and miR455-5P are significantly downregulated in placentas from preeclampsia patients, whereas other placenta-specific microRNAs remain unaffected. microRNA target prediction and validation revealed a potential link of miR455-3P to hypoxia signaling. Together with our observation that expression levels of miR455-3P and miR455-5P are upregulated during trophoblast differentiation, our results suggest a model in which miR455-3P represses a hypoxia response that might otherwise prevent cytotrophoblasts from syncytiotrophoblast differentiation. In summary, our work reveals aberrant hypoxia signaling in preeclampsia that can be explained by deregulated expression of miR455. As miR455 has been found in circulating blood, the development of noninvasive prenatal tests enabling early diagnosis of preeclampsia may be possible.
authors.affiliation: Laboratory for Prenatal Medicine, Department of Biomedicine, University Hospital Basel, Basel CH-4031, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Lalevée
authors.affiliation: 1] Laboratory for Prenatal Medicine, Department of Biomedicine, University Hospital Basel, Basel CH-4031, Switzerland [2] Department of Obstetrics and Gynecology, University Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Lapaire
authors.affiliation: 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Bühler
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D024022:Fibrillar Collagens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018396:Mucin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D006063:Chorionic Gonadotropin; D005576:Colforsin; D024022:Fibrillar Collagens; D035683:MicroRNAs; D018396:Mucin-1; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D000099162:Endothelial PAS Domain-Containing Protein 1; C480971:COL27A1 protein, human; C583404:MIRN455 microRNA, human