Expression patterns of microRNAs in the chorioamniotic membranes: a role for microRNAs in human pregnancy and parturition

Abstract

MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression during development. This study was performed to determine gestational age-dependent changes in miRNA expression in the chorioamniotic membranes and to assess the significance of miRNAs in human pregnancy and parturition. The expression profile of 455 miRNAs was compared between patients at term without labor (TNL: n=10), in labor (TL: n=10), and preterm labor (PTL: n=10) using microarrays. A total of 39 miRNAs were differentially expressed between term and preterm cases, of which 31 (79.5%) were down-regulated at term. Expression of 10 miRNAs, including miR-338, differentially expressed between PTL and TL groups was decreased at term. Computational analyses using miRBase Targets have identified PLA2G4B, a phospholipase implicated in parturition, as a putative target of miR-338. Inhibition of endogenous miR-338 with anti-miR-338 increased the mRNA and protein expression of PLA2G4B in decidual cells. Luciferase assay with reporter constructs confirmed that the suppression of PLA2G4B occurs through binding of miR-338 to the 3’UTR of PLA2G4B. Interestingly, the expression of Dicer, a key miRNA-processing enzyme, was markedly decreased at term, particularly with labor in the chorioamniotic membranes. Collectively, the novel findings reported herein strongly suggest that post-transcriptional regulation of genes by miRNAs, coupled with the changes of miRNA processing machinery in the chorioamniotic membranes, plays a role in pregnancy and parturition. Furthermore, the expression level of Dicer in the chorioamniotic membranes dichotomizes pathological preterm labor and physiological spontaneous labor at term.

Downregulation of Human Farnesoid X Receptor by miR-421 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells

“…In this study, we showed that FXR is a novel target of miR-421 in HCC cells, and downregulation of FXR may be a new oncogenic mechanism of miR-421. miRNAs can target mRNAs at the 3 0 -UTR/5 0 -UTR, even at the open reading frame (ORF) by partial sequence homology, leading to translation repression/mRNA degradation (20)(21)(22). The current miRNA databases, such as miRBase, TargetScan, miRanda, and so on, are usually used for predicting the miRNAs for a target gene or predicting the targets of a miRNA based on the 3 0 -UTR sequences of mRNAs.…”

Prevention of preterm birth: Harnessing science to address the global epidemic

“…The expression of other miRNAs in the placenta, chorioamniotic membranes, or cervix has also been associated with increased risk of PTB (33,34). The targets and mechanism of action of these miRNAs remain largely unknown.…”

MicroRNAs, immune cells and pregnancy

“…We are only beginning to discover the roles of miRNAs in reproduction. miRNAs have been implicated in endometrial receptivity, [34][35][36] implantation, 37-42 labor [43][44][45][46][47] and even spontaneous fetal loss in the pig. 48,49 In the uterus, most of the physiological changes occurring over the estrous/menstrual cycle and during pregnancy are driven by the ovarian hormones.…”