title: miR-141 contributes to fetal growth restriction by regulating PLAG1 expression.
abstract: BACKGROUND
  Fetal growth restriction (FGR) is an important but poorly understood condition of pregnancy, which results in significant fetal, neonatal and long-term morbidity and mortality. Novel research has suggested that altered miRNA expression in the plasma and placenta is associated with adverse pregnancy. We hypothesized that aberrant expression of microRNA-141 (miR-141) in the placenta is associated with FGR. Additionally, expression levels of predicted target genes of miR-141 were also analyzed in placental tissues of FGR and normal controls.
  
  
  RESULTS
  Using quantitative real time PCR, we analyzed the expression level of miR-141 and its target genes in placentas of FGR pregnancies (n = 21) and normal controls (n = 34). Western blot was used to detect the protein expression level of the target genes of miR-141. MiR-141 showed significant up regulation in FGR and significant down regulation of its targets, i.e. E2F transcription factor 3 (E2F3) protein, pleiomorphic adenoma gene 1 (PLAG1) mRNA and protein. Moreover, a positive correlation was found between PLAG1 and insulin-like growth factor 2 (IGF2) expression levels (Spearman r = 0.56, p<0.0001). MiR-141 yields an AUC of 0.83 with 88.5% sensitivity and 71.7% specificity for separating FGR from normal controls. This study indicates that miR-141 may be diagnostically important in FGR.
  
  
  CONCLUSIONS
  Our results indicate that aberrant high expression level of miR-141 might play important roles in the pathogenesis of FGR by suppressing E2F3 and PLAG1. We propose that miR-141 may participate in a miR-141-PLAG1-IGF2 network relating to FGR development. These findings may provide new targets via miR-141 in diagnosis and therapy of FGR in the future.
authors.affiliation: Department of Obstetrics, Wuxi Hospital for Maternal and Child Health Care, Wuxi, China.
authors.forename: Qiuqin
authors.initials: Q
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gao
authors.forename: Huijuan
authors.initials: H
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D012372:ROC Curve; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; C104382:PLAG1 protein, human; D007335:Insulin-Like Growth Factor II
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