miR-210 Inhibits Trophoblast Invasion and Is a Serum Biomarker for Preeclampsia

Abstract

Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P < 0.0001, area under the receiver operator curve = 0.89). Hence, we conclude that aberrant expression of miR-210 may contribute to trophoblast function and that miR-210 is a novel predictive serum biomarker for preeclampsia that can help in identifying at-risk women for monitoring and treatment.

Dysregulated circulating miRNAs in preeclampsia

“…Notably, miR-210, which is one of the more commonly recurring miRNAs overexpressed in PE (22,(32)(33)(34)(35)(36), was also elevated in our PE cohort. This particular miR-210 has been identified as a hypoxia-induced miRNA in many cell types and tissues and is consistently upregulated by hypoxia in both physiological and malignant conditions (37,38).…”

“…However, the use of RNU6B complements technical bias with biological bias. Although RNU6B does not necessarily represent the 'best' reference, it has been previously used to analyse miRNAs in the sera of preeclamptic women (23,32). The selection of the patients included in different studies may also introduce some bias.…”

MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of differentiation 1 in glioblastoma cells

“…MiR-210 has been shown to be involved in angiogenesis, DNA damage response, invasion, proliferation, apoptosis, and the cell cycle. Anton et al [1] reported that miR-210 is upregulated in preeclamptic placentas, and that it regulates cell viability. MiR-210 overexpression was shown to reduce trophoblast invasion, while miR-210 inhibition promoted invasion.…”

Role of Biomarkers in Early Detection of Preeclampsia

“…Recently, several miRNA were found to be deregulated in placentas of PE patients and they seemed to be closely associated with early pathogenesis. One such miRNA is miR-210, a novel predictive serum biomarker for preeclampsia, that can help in identifying at-risk women for monitoring and treatment [42].…”