H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating T?R3 in placentae with fetal growth restriction.

ABSTRACT: Fetal growth restriction (FGR) is a well-recognized risk factor for perinatal mortality and morbidity, as well as neurodevelopmental impairment and adulthood onset disorders. Here we report that the H19 long noncoding RNA (lncRNA) is significantly decreased in placentae from pregnancies with FGR. Downregulation of H19 leads to reduced migration and invasion of extravillous trophoblast (EVT) cells in vitro. This is consistent with reduced trophoblast invasion that has been observed in FGR. Genome-scale transcriptome profiling of EVT cells reveals significantly decreased expression of the type III TGF-? receptor (T?R3) following H19 knockdown. Decreased T?R3 expression is also seen in FGR placentae. T?R3 repression decreases EVT cell migration and invasion, owing to impaired TGF-? signaling through a non-canonical TGF-? signaling pathway. Further, we identify T?R3 as a novel regulatory target of microRNA let-7. We propose that dysregulation of this newly identified H19/T?R3-mediated regulatory pathway may contribute to the molecular mechanism of FGR. Our findings are the first to show a lncRNA-based mechanism of FGR, holding promise for the development of novel predictive, diagnostic, and therapeutic modalities for FGR.

SUBMITTER: Zuckerwise L 

PROVIDER: S-EPMC5122399 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature