Dysregulated circulating miRNAs in preeclampsia

Abstract

Abstract. Preeclampsia (PE) is a pregnancy-related disease with potentially severe consequences with respect to foeto-maternal morbidity and mortality. However, the molecular pathogenesis of PE remains largely unknown. Recent reports have shown that microRNAs (miRNAs or miRs) may play important roles in the development of PE. Analysing the miRNAs in sera from preeclamptic women may improve our understanding of the pathophysiological mechanisms of the disease. The aim of this retrospective study was to identify whether circulating miRNAs were differentially expressed in PE patients compared with controls. Serum samples from 23 women who developed PE were compared with samples from 44 pregnant controls. Seventeen circulating miRNAs previously described in PE were chosen for evaluation of their expression by reverse transcription quantitative polymerase chain reaction (RT-qPCR). In the maternal serum, the miR-210-3p, miR-210-5p, miR-1233-3p, and miR-574-5p levels were found to be significantly higher in the PE patients than in the controls (P<0.05). Using a logistic regression model, we evaluated the discriminant power of those differentially expressed miRNAs, and the combination of miR-210-5p and miR-574-5p yielded an area under the curve of 0.7223 for discriminating PE patients from the controls. In conclusion, the fact that four circulating miRNAs (miR-210-3p, miR-210-5p, miR-1233-3p, and miR-574-5p) were differentially expressed in the sera of women who developed PE compared with controls confirms the possible pathophysiological role of miRNAs in PE.

Cadmium inhibits placental trophoblast cell migration via miRNA regulation of the transforming growth factor beta (TGF-β) pathway

“…In the same study, placental trophoblast cells treated with Cd displayed increased expression of the TGF-β pathway and dysregulation of TGF-β-targeting miRNAs following Cd treatment. These data support that the TGF-β pathway may be controlled epigenetically and showcase epigenetic dysfunction as a hallmark of PE 12 . Cd may also play a role in influencing cell migration, where treatment with Cd previously inhibited in vitro migration in immortalized human trophoblast cells (HTR-8/SVneo) through actin skeleton reorganization 13 , a possible effect of Cd-induced expression of the TGF-β pathway.…”

“…In contrast, migration was comparable to control cells in placental cells overexpressing miR-26a with or without Cd treatment. miRNA dysfunction is a hallmark of PE 12 and is postulated as a cause due to miRNAs being critical regulators of cell function by mediating gene expression. In addition, numerous members of the TGF-β pathway are targeted by miRNAs 25 further underlying the importance of understanding the mechanism of miRNA-mediated PE.…”

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

“…MiRNAs regulate mRNA, which encode proteins that modulate cellular functions, by binding to the untranslated region (3′UTR) of target mRNAs. As a result, target gene expression can be regulated post‐transcriptionally through degradation of target mRNAs . Therefore, miRNAs play important roles in physiological homoeostasis in health and pathophysiological dysregulation in disease .…”

“…As a result, target gene expression can be regulated post‐transcriptionally through degradation of target mRNAs . Therefore, miRNAs play important roles in physiological homoeostasis in health and pathophysiological dysregulation in disease . To date, more than 1000 miRNAs have been validated in humans, among which more than 600 miRNAs are expressed in the human placenta .…”

“…To date, more than 1000 miRNAs have been validated in humans, among which more than 600 miRNAs are expressed in the human placenta . Abnormal expression of specific miRNAs has been reported in various studies of human diseases, including PE . Comparative analysis between PE placentas and normal placentas identified 11 up‐regulated and 23 down‐regulated miRNAs .…”