miR-141 Contributes to Fetal Growth Restriction by Regulating PLAG1 Expression

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.