High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia

Wang, Yonghong; Yang, Xukui; Yang, Yuanyuan; Wang, Wenjun; Zhao, Meiling; Liu, Huiqiang; Li, Dongyan; Hao, Min

doi:10.1038/jp.2015.192

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…More recently, exosomal microRNAs (exomiRNA), in particular, have emerged as key biomarkers of several other disease states, as they are selectively packaged into exosomes15 and are subsequently released by the cell, destined to participate in cellular reprogramming 16,17. A few studies have described the key physiological role of miRNAs in regulating normal placental development, as well as the pathogenesis of PE,18–22 leading to our proposal that a comprehensive understanding of exosomal miRNA will provide key functional insights into the role of these nanovesicles in the pathophysiology of PE.…”

Section: Introductionmentioning

confidence: 99%

<p>Exosomal microRNA profiling in early and late onset preeclamptic pregnant women reflects pathophysiology</p>

Pillay¹,

Vatish²,

Duarte³

et al. 2019

IJN

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Background: Preeclampsia is the leading cause of maternal and fetal mortality due to the inability to diagnose and treat the disorder early in pregnancy. This is attributed to the complex pathophysiology and unknown etiology of the disorder, which is modulated by several known and unknown factors. Exosomes have recently been implicated as possible mediators of the pathogenesis of preeclampsia, with, however, no evidence linking these nanovesicles to the pathophysiology of preeclampsia and its subtypes. Methods: To better understand the pathophysiological role of exosomes in preeclampsia, we have analyzed the exosomal microRNA in early and late onset preeclamptic women in comparison to their gestationally matched normotensive controls using Digital Direct Detection (NanoString Technologies). Results: For the first time, distinct exosomal microRNA signatures in early and late onset preeclampsia have been identified. Moreover, these signatures indicate that exosomes are involved in key pathological features associated with preeclampsia and differentiate between the subtypes. Conclusion: This study forms the basis for the diagnostic and functional validation of the identified signatures as biomarkers of preeclampsia and its subtypes.

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Section: Introductionmentioning

confidence: 99%

<p>Exosomal microRNA profiling in early and late onset preeclamptic pregnant women reflects pathophysiology</p>

Pillay¹,

Vatish²,

Duarte³

et al. 2019

IJN

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“…The 8 top‐ranked up‐ and downregulated DE miRNAs [8/31] in pregnant women who developed PE as compared to those who continued a normal pregnancy were all previously reported in association with PE (upregulated: mir‐885, mir‐122, mir‐34a and mir‐182; downregulated: mir‐29a, mir‐27a, mir‐133a and mir‐424) 16,60–66 . Seventy‐five per cent [12/16 = 75%] of PE‐vitamin D‐associated DE miRNAs had prior evidence in differential expression in circulating blood and/or placenta of pregnant women with PE as compared to those of normal pregnancies 60–63,65,67–86 . Table S2 provides existing evidence in the literature for the association of each of these 16 DE miRNAs with PE in the literature.…”

Section: Resultsmentioning

confidence: 99%

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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“…miR-122 plays a role in metabolic diseases, in particular in the development of gestational diabetes mellitus (GDM) [ 44 , 45 ]. Also miR-122-5p increases in leukocytes [ 46 ] and placental tissue [ 47 ] in patients with PE. In addition, in our previous study, we found that hsa-miR-122-5p has the highest level of expression in plasma in healthy pregnant women [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma miRNA Profile in High Risk of Preterm Birth during Early and Mid-Pregnancy

Илларионов

Pachuliia

Vashukova

et al. 2022

Genes

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In recent years evidence has been accumulated showing that miRNAs can act as potential biomarkers or targets for therapy of preterm birth, one of the most important problems in modern obstetrics. We have performed a prospective study of the miRNA profile in the plasma during the first and second trimesters in pregnant women with high risk of preterm birth (n = 13 cases and n = 11 controls). For the study group plasma blood samples at 9–13 weeks before diagnosis and at 22–24 weeks after start of therapy were selected. Using high-throughput sequencing technology we detected differences in the levels of 15 miRNAs (3 upregulated—hsa-miR-122-5p, hsa-miR-34a-5p, hsa-miR-34c-5p; 12 downregulated—hsa-miR-487b-3p, hsa-miR-493-3p, hsa-miR-432-5p, hsa-miR-323b-3p, hsa-miR-369-3p, hsa-miR-134-5p, hsa-miR-431-5p, hsa-miR-485-5p, hsa-miR-382-5p, hsa-miR-369-5p, hsa-miR-485-3p, hsa-miR-127-3p) (log2(FC) ≥ 1.5; FDR ≤ 0.05) during the first trimester compared with the control (non-high-risk of preterm birth pregnant women). All downregulated miRNAs in the first trimester from the placenta-specific C14MC cluster. During the second trimester no differentially expressed miRNAs were found. Our results suggest that the miRNA profile in plasma during early pregnancy may predict a high risk of preterm birth, which is important in preventing gestational problems as early as possible.

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High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia

Cited by 10 publications

References 46 publications

<p>Exosomal microRNA profiling in early and late onset preeclamptic pregnant women reflects pathophysiology</p>

<p>Exosomal microRNA profiling in early and late onset preeclamptic pregnant women reflects pathophysiology</p>

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

Plasma miRNA Profile in High Risk of Preterm Birth during Early and Mid-Pregnancy

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