Potential role of circulating microRNAs as early markers of preeclampsia

Ura, Blendi; Feriotto, Giordana; Monasta, Lorenzo; Bilel, Sabrine; Zweyer, Marina; Celeghini, Claudio

doi:10.1016/j.tjog.2014.03.001

Cited by 92 publications

(119 citation statements)

References 26 publications

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“…There was also a higher level of circulating miR-1233 in the group of women who developed PE compared with the group of women with a normal pregnancy. Our results confirmed those of Ura et al (23), who were the first researchers to identify a potential role for miR-1233, which has already been described in renal carcinoma, in predicting PE. It is important to note that both miR-1233 and miR-210, which are upregulated in PE, are also upregulated in renal cell carcinoma.…”

Section: Discussionsupporting

confidence: 92%

“…In the present study, we confirmed the differential expression of several miRNAs that were identified in previous studies (20)(21)(22)(23). Of the 17 miRNAs selected, miR-210-3p, miR-210-5p, miR-1233-3p, and miR-574-5p were upregulated in the sera of women who later developed PE compared with the controls who did not develop PE according to RT-qPCR.…”

Section: Discussionsupporting

confidence: 90%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Specific plasma-related miRNAs were identified in maternal plasma or serum in normal pregnancies, as well as in pathological pregnancy conditions, such as PE (18,19). Several recent reports described the significant dysregulation of specific miRNA expression in the maternal circulation of PE patients compared with controls (miR-24, miR-26a, miR-29a, miR-103, miR-130b, miR-141, miR-144, miR-152, miR-181a, miR-210, miR-342-3p, miR-520, miR-574-5p, and miR-1233) (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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Dysregulated circulating miRNAs in preeclampsia

et al. 2016

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dysregulated circulating miRNAs in preeclampsia

et al. 2016

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“…The more unambiguously identified ECFCs, based on well-known endothelial markers and functional properties, may be needed to confirm the levels or roles of circulating ECFCs in the peripheral blood of pregnant women with preeclampsia, because many biomarkers have been used in an attempt to provide a much more effective tool in predicting the risk of occurrence of preeclampsia. 10 …”

mentioning

confidence: 99%

Endothelial cell dysfunction and preeclampsia

Wang¹,

Yang²,

Chen³

et al. 2015

Journal of the Chinese Medical Association

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Integration of circulating microRNAs and transcriptome signatures identifies early‐pregnancy biomarkers of preeclampsia

Mirzakhani,

Handy,

et al. 2023

Clinical & Translational Med

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BackgroundMicroRNAs (miRNAs) have been implicated in the pathobiology of preeclampsia, a common hypertensive disorder of pregnancy. In a nested matched case‐control cohort within the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we previously identified peripheral blood mRNA signatures related to preeclampsia and vitamin D status (≤30 ng/mL) during gestation from 10 to 18 weeks, using differential expression analysis.MethodsUsing quantitative PCR arrays, we conducted profiling of circulating miRNAs at 10–18 weeks of gestation in the same VDAART cohort to identify differentially expressed (DE) miRNAs associated with preeclampsia and vitamin D status. For the validation of the expression of circulating miRNA signatures in the placenta, the HTR‐8/SVneo trophoblast cell line was used. Targets of circulating miRNA signatures in the preeclampsia mRNA signatures were identified by consensus ranking of miRNA‐target prediction scores from four sources. The connected component of target signatures was identified by mapping to the protein‐protein interaction (PPI) network and hub targets were determined. As experimental validation, we examined the gene and protein expression of IGF1R, one of the key hub genes, as a target of the DE miRNA, miR‐182‐5p, in response to a miR‐182‐5p mimic in HTR‐8/SVneo cells.ResultsPregnant women with preeclampsia had 16 circulating DE miRNAs relative to normal pregnancy controls that were also DE under vitamin D insufficiency (9/16 = 56% upregulated, FDR < .05). Thirteen miRNAs (13/16 = 81.3%) were detected in HTR‐8/SVneo cells. Overall, 16 DE miRNAs had 122 targets, of which 87 were unique. Network analysis demonstrated that the 32 targets of DE miRNA signatures created a connected subnetwork in the preeclampsia module with CXCL8, CXCL10, CD274, MMP9 and IGF1R having the highest connectivity and centrality degree. In an in vitro validation experiment, the introduction of an hsa‐miR‐182‐5p mimic resulted in significant reduction of its target IGF1R gene and protein expression within HTR‐8/SVneo cells.ConclusionsThe integration of the circulating DE miRNA and mRNA signatures associated preeclampsia added additional insights into the subclinical molecular signature of preeclampsia. Our systems and network biology approach revealed several biological pathways, including IGF‐1, that may play a role in the early pathophysiology of preeclampsia. These pathways and signatures also denote potential biomarkers for the early stages of preeclampsia and suggest possible preventive measures.

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Potential role of circulating microRNAs as early markers of preeclampsia

Abstract: Circulating miRNAs deserve further investigation in order to explore their potential role in the pathogenesis of preeclampsia. In particular, miR-1233 might represent a potential marker of early sPE.

Cited by 92 publications

References 26 publications

Dysregulated circulating miRNAs in preeclampsia

Dysregulated circulating miRNAs in preeclampsia

Endothelial cell dysfunction and preeclampsia

Integration of circulating microRNAs and transcriptome signatures identifies early‐pregnancy biomarkers of preeclampsia

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