Abstract
Our understanding of how microRNAs (miRNAs) regulate gene networks and affect different molecular pathways leading to various human pathologies has significantly improved over the years. In contrary, the role of miRNAs in pregnancy-related hypertensive disorders such as preeclampsia (PE) is only beginning to emerge. Recent papers highlight that adverse pregnancy outcomes are associated with aberrant expression of several miRNAs. Presently, efforts are underway to determine the biologic function of these placental miRNAs which can shed light on their contribution to these pregnancy-related disease conditions. The discovery that miRNAs are stable in circulation coupled with the fact that the placenta is capable of releasing them to the circulation in exosomes generates a lot of enthusiasm to use them as biomarkers. In this review, we will summarize the recent findings of our understanding of miRNA regulation in relation to PE, a hypertensive disorder of pregnancy. Particular emphasis will be given to the role of key miRNA molecules such as miR-210 and miR-155 that are known to be consistently dysregulated in women with PE.
Highlights
Preeclampsia (PE) is a multisystem pregnancy disorder that affects about 10 million women globally [1]
We reported that activation of toll-like receptor 3 (TLR3) via poly I:C produces the PE-like symptoms of hypertension, endothelial dysfunction, and proteinuria in mice only when pregnant
cysteine-rich protein 61 (CYR61) is known to induce the expression of vascular endothelial growth factor (VEGF) and this group hypothesized that a decrease in CYR61 would cause a decrease in VEGF levels in placentas with PE. miR155 targeted a region within the 3′UTR sequence of the CYR61 gene which leads to decreased levels of CYR61 in PE placentas. These findings propose a miR-155-CYR61-VEGF pathway where an overexpression of miR-155 causes a downregulation of CYR61 which leads to decreased levels of VEGF, reducing placental angiogenesis
Summary
Preeclampsia (PE) is a multisystem pregnancy disorder that affects about 10 million women globally [1]. MicroRNAs are small (~22–25 nt), endogenous, single-stranded, non-coding RNAs that regulate gene expression preferentially by binding to the untranslated region (3′UTR) of a target gene [8] These regulatory molecules play an important role in the post-transcriptional regulation of gene expression by causing translational inhibition or mRNA cleavage thereby silencing gene expression unlike protein-coding genes [9]. If Drosha is knocked down in spermatogenic cells in postnatal testes using Cre-Lox, spermatogenesis is disrupted [22] The role of another protein DGCR8 involved in the miRNA biogenesis pathway that interacts with Drosha to produce pre-miRNA in the nucleus is determined using a conditional knockout mouse model. This is largely due to the fact that a mouse deficient in any of the miRNA biogenesis proteins often exhibit early developmental defects prior to placenta formation
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