title: miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.
abstract: Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P < 0.0001, area under the receiver operator curve = 0.89). Hence, we conclude that aberrant expression of miR-210 may contribute to trophoblast function and that miR-210 is a novel predictive serum biomarker for preeclampsia that can help in identifying at-risk women for monitoring and treatment.
authors.affiliation: Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Lauren
authors.initials: L
authors.lastname: Anton
authors.affiliation: Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Olarerin-George
authors.affiliation: Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Nadav
authors.initials: N
authors.lastname: Schwartz
authors.affiliation: Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sindhu
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jamie
authors.initials: J
authors.lastname: Bastek
authors.affiliation: Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: John B
authors.initials: JB
authors.lastname: Hogenesch
authors.affiliation: Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: melovitz@obgyn.upenn.edu.
authors.forename: Michal A
authors.initials: MA
authors.lastname: Elovitz
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002465:Cell Movement; D015331:Cohort Studies; D003710:Demography; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D011225:Pre-Eclampsia / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000235:genetics; D014327:Trophoblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015415:Biomarkers; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D048049:Extracellular Signal-Regulated MAP Kinases
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