miR-31-5p from placental and peripheral blood exosomes is a potential biomarker to diagnose preeclampsia

Zou, Gang; Ji, Qingfang; Geng, Zixiang; Du, Xin; Jiang, Lingyan; Liu, Te

doi:10.1186/s41065-022-00250-z

Cited by 8 publications

(4 citation statements)

References 36 publications

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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%

“… 16 , 60 , 61 , 62 , 63 , 64 , 65 , 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 , 61 , 62 , 63 , 65 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 Table S2 provides existing evidence in the literature for the association of each of these 16 DE miRNAs with PE in the literature. This observation was further substantiated by the evidence from microRNA Tissue Expression Database (miTED).…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

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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“…Exosomal miR‐195 ameliorated hypoxia‐induced cell damage in UC‐MSCs via TFPI2, suggesting a potential treatment strategy for PE 115 . Exosome‐derived miR‐31‐5p was found to have a strong correlation with several common diagnostic indications of PE, according to research by Zou et al 116 These findings imply that miR‐31‐5p may be a useful biomarker for monitoring the development of PE. miR‐31‐5p controls the TGF‐β signaling pathway and has an impact on the epithelial‐mesenchymal transition (EMT).…”

Section: Immunomodulatory Effects Of Mscs‐derived Exosome For Pe Therapymentioning

confidence: 92%

Mesenchymal stem cell‐derived exosomes in preeclampsia: A next‐generation therapeutic tool

Margiana

2024

Cell Biochemistry & Function

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Preeclampsia (PE) is a major gestational disorder that causes both long‐ and short‐term damage to both the mother and the fetus. Endometrium decidualization and the formation of the placenta are orchestrated by mesenchymal stem cells (MSCs). MSCs obtained from patients with PE exhibit an elevated rate of aging and apoptosis, which impairs the interplay between MSCs and endothelium, trophoblast, and immune cells in the placenta, accelerating the onset of PE. Preclinical and clinical evidence imply that the MSC‐based therapy approach for PE is prospective. Importantly, as a novel cell‐free approach, MSC‐derived exosomes can improve symptoms and maternal–fetal survival in PE models by raising cell metabolism, encouraging angiogenesis balance, and regulating immune responses. Even following allogeneic administration, the likelihood of immune rejection is very limited as a result of the small quantity of exosome membrane‐bound proteins. Furthermore, because exosomes do not expand, developing tumors is not probable. As a result, MSC‐derived exosomes show superiority over MSCs in terms of safety. For the first time, we outline the properties of MSC‐exosomes and highlight their functions and potential as a new paradigm for PE therapy in this review.

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“…Recently, numerous investigations have been published describing the putative roles of various small RNAs in PE, but the overlap among these predicted targets is typically small (33,(53)(54)(55)(56)(57)(58)(59). Apart from technical differences, a major concern with these investigations is that the included patient groups in these studies were not generally uniform due to the inherent heterogeneity of the disease.…”

Section: Introductionmentioning

confidence: 99%

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

Gál,

Fóthi,

Orosz

et al. 2024

Front. Immunol.

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IntroductionPreeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR.MethodsWe isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis.ResultsOverall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR.DiscussionOur rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.

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miR-31-5p from placental and peripheral blood exosomes is a potential biomarker to diagnose preeclampsia

Cited by 8 publications

References 36 publications

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

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

Mesenchymal stem cell‐derived exosomes in preeclampsia: A next‐generation therapeutic tool

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia

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