Analysis of Circulating C19MC MicroRNA as an Early Marker of Hypertension and Preeclampsia in Pregnant Patients: A Systematic Review

Kondracka, Adrianna; Jaszczuk, Ilona; Koczkodaj, Dorota; Kondracki, Bartosz; Frąszczak, Karolina; Oniszczuk, Anna; Rybak-Krzyszkowska, Magda; Staniczek, Jakub; Filip, Agata; Kwaśniewska, Anna

doi:10.3390/jcm11237051

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…PE affects 2-8% of all pregnancies worldwide (7,29), leading to the deaths of more than 75,000 women and 500,000 fetuses annually (4), but as the symptoms can usually be detected only in the second half of gestation, early detection of the disease using appropriate biomarkers remains a challenge. Recently, several studies have proposed the role of non-coding RNAs (ncRNAs) in the etiology of PE (30)(31)(32)(33), and an emerging view is that these molecules could be transported in the circulation in membrane-encapsulated extracellular vesicles (EVs) and thus have diagnostic significance (34)(35)(36)(37)(38)(39)(40). Among the ncRNA groups, small RNAs of the RNA interference (RNAi) pathways are attractive targets for investigation because their functional roles have been more extensively elucidated as opposed to other classes, such as long ncRNAs or Y RNAs (31,41).…”

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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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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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Circulating extracellular vesicular microRNA signatures in early gestation show an association with subsequent clinical features of pre-eclampsia

Ghosh,

Thamotharan,

Fong

et al. 2024

Sci Rep

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In a prospective cohort of subjects who subsequently developed preeclampsia (PE, n = 14) versus remaining healthy (NORM, n = 12), early gestation circulating extracellular vesicles (EVs) containing a panel of microRNA signatures were characterized and their biological networks of targets deciphered. Multiple microRNAs of which some arose from the placenta (19MC and 14MC) demonstrated changes in association with advancing gestation, while others expressed were pathognomonic of the subsequent development of characteristic clinical features of PE which set in as a late-onset subtype. This panel of miRNAs demonstrated a predictability with an area under the curve of 0.96 using leave-one-out cross-validation training in a logistic regression model with elastic-net regularization and precautions against overfitting. In addition, this panel of miRNAs, some of which were previously detected in either placental tissue or as maternal cell-free non-coding transcripts, lent further validation to our EV studies and the observed association with PE. Further, the identified biological networks of targets of these detected miRNAs revealed biological functions related to vascular remodeling, cellular proliferation, growth, VEGF, EGF and the PIP3/Akt signaling pathways, all mediating key cellular functions. We conclude that we have demonstrated a proof-of-principle by detecting a panel of EV packaged miRNAs in the maternal circulation early in gestation with possibilities of biological function in the placenta and other maternal tissues, along with the probability of predicting the subsequent clinical appearance of PE, particularly the late-onset subtype.

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Urinary miRNA Expression in Pre-Eclampsia During Early and Mid-Pregnancy

Illarionov,

Maltseva,

Pachuliia

et al. 2024

ncRNA

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Background: Pre-eclampsia (PE) is a serious condition affecting 2–8% of pregnancies worldwide, leading to high maternal and fetal morbidity and mortality. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as potential biomarkers for various pregnancy-related pathologies, including PE. MiRNAs in plasma and serum have been extensively studied, but urinary miRNAs remain underexplored, especially during early pregnancy. This study aimed to investigate the urinary miRNA expression profiles in women with pre-eclampsia during the first and second trimesters. Materials and Methods: A prospective study was conducted using 48 urine samples from 24 pregnant women (n = 12 pre-eclampsia and n = 12 controls). Urine samples were collected in the first (9–13 weeks) and second (22–24 weeks) trimesters. MiRNA isolation, library preparation, and high-throughput sequencing were performed, followed by differential expression and enrichment analyses. Results: In the first trimester, five miRNAs were dysregulated in PE in comparison with the control group (hsa-miR-184, hsa-miR-203a-3p, hsa-miR-205-5p, hsa-miR-223-3p—downregulated; hsa-miR-1-3p—upregulated). In the second trimester, hsa-miR-205-5p and hsa-miR-223-3p were downregulated, and hsa-miR-9-5p, hsa-miR-1-3p, and hsa-miR-206 were upregulated. Conclusions: Our study identified differentially expressed miRNAs in the urine of pre-eclamptic patients during early pregnancy. These findings suggest that specific urinary miRNAs could serve as non-invasive biomarkers for the early detection and risk assessment of pre-eclampsia. The changes in the level of differential expression of miRNAs during gestation highlight their role in the progression of PE. Further research and validation with a larger cohort are needed to explore their clinical potential for improving maternal and fetal outcomes through early intervention.

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Analysis of Circulating C19MC MicroRNA as an Early Marker of Hypertension and Preeclampsia in Pregnant Patients: A Systematic Review

Cited by 3 publications

References 28 publications

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

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

Circulating extracellular vesicular microRNA signatures in early gestation show an association with subsequent clinical features of pre-eclampsia

Urinary miRNA Expression in Pre-Eclampsia During Early and Mid-Pregnancy

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