title: Distinct cervical microRNA profiles are present in women destined to have a preterm birth.
abstract: OBJECTIVE
  Although premature cervical remodeling is involved in preterm birth (PTB), the molecular pathways that are involved have not been elucidated fully. MicroRNAs (miRNAs) that are highly conserved single-stranded noncoding RNAs that play a crucial role in gene regulation have now been identified as important players in disease states. The objective of this study was to determine whether miRNA profiles in cervical cells are different in women who are destined to have a PTB compared with a term birth.
  
  
  METHODS
  A nested case-control study was performed. With the use of a noninvasive method, cervical cells were obtained at 2 time points in pregnancy. The cervical cell miRNA expression profiles were compared between women who ultimately had a PTB (n = 10) compared with a term birth (n = 10). MiRNA expression profiles were created with the Affymetrix GeneChip miRNA Array. The data were analyzed with the Significance of Analysis of Microarrays and Principle Components Analyses. A false-discovery rate of 20% was used to determine the most differentially expressed miRNAs. Validation was performed with quantitative polymerase chain reaction. In vitro studies were performed to confirm expression and regulation of select miRNAs.
  
  
  RESULTS
  With a false-discovery rate of 20% of the 5640 miRNAs that were analyzed on the array, 99 miRNAs differed between those with a PTB vs a term birth. Qualitative polymerase chain reaction validated the array findings. In vitro studies confirmed expression of select miRNAs in cervical cells.
  
  
  CONCLUSIONS
  MiRNA profiles in cervical cells may distinguish women who are at risk for PTB months before the outcome. With the large downstream effects of miRNAs on gene expression, these studies provide a new understanding of the processes that are involved in premature cervical remodeling and allow for the discovery of new therapeutic targets.
authors.affiliation: Maternal-Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Michal A
authors.initials: MA
authors.lastname: Elovitz
authors.affiliation: Maternal-Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Amy G
authors.initials: AG
authors.lastname: Brown
authors.affiliation: Maternal-Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Anton
authors.affiliation: Maternal-Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Gilstrop
authors.affiliation: Maternal-Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Laura
authors.initials: L
authors.lastname: Heiser
authors.affiliation: Maternal-Child Health Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Bastek
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs
keywords: cervical remodeling; ectocervical cells; microRNA; preterm birth