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Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p
MicroRNAs (miRNAs) play an important role in the pathophysiology of preeclampsia (PE). However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression prof...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493119/ https://www.ncbi.nlm.nih.gov/pubmed/34630130 http://dx.doi.org/10.3389/fphys.2021.678184 |
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author | Luizon, Marcelo R. Conceição, Izabela M. C. A. Viana-Mattioli, Sarah Caldeira-Dias, Mayara Cavalli, Ricardo C. Sandrim, Valeria C. |
author_facet | Luizon, Marcelo R. Conceição, Izabela M. C. A. Viana-Mattioli, Sarah Caldeira-Dias, Mayara Cavalli, Ricardo C. Sandrim, Valeria C. |
author_sort | Luizon, Marcelo R. |
collection | PubMed |
description | MicroRNAs (miRNAs) play an important role in the pathophysiology of preeclampsia (PE). However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using a PCR array in plasma collected between 20 and 25 weeks of gestation from pregnant women, who subsequently developed PE and those who remained healthy during pregnancy, randomly selected from a prospective cohort. Overall, 23 miRNAs had a fold change > 2.0 and were considered to be upregulated in plasma from pregnant women who subsequently developed PE, even before the onset of clinical symptoms of PE. However, only miR-204-5p was statistically significant (P = 0.0082). Experimentally validated interactions for the target genes of miR-204-5p extracted from miRTarBase were used in the gene set functional enrichment analysis to identify Reactome pathways. The network connecting the 37 target genes for miR-204-5p revealed pathways of known pathophysiological relevance during the early development of PE and included key genes related to PE, such as BDNF, MMP-9, MALAT1, TGFBR2, and SIRT1. We further depicted downstream targets of SIRT1 that are related to the vascular endothelial function or implicated in the pathophysiology of PE, namely, FOXO1, NFκB, HIF-1α, NOS3, and PPAR-γ. Our novel findings provide for circulating miRNAs upregulated in the second trimester on plasma from pregnant women who subsequently developed PE that is potentially related to the early development of PE, which may guide further studies focused on the validation of potential predictive biomarkers in PE. |
format | Online Article Text |
id | pubmed-8493119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84931192021-10-07 Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p Luizon, Marcelo R. Conceição, Izabela M. C. A. Viana-Mattioli, Sarah Caldeira-Dias, Mayara Cavalli, Ricardo C. Sandrim, Valeria C. Front Physiol Physiology MicroRNAs (miRNAs) play an important role in the pathophysiology of preeclampsia (PE). However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using a PCR array in plasma collected between 20 and 25 weeks of gestation from pregnant women, who subsequently developed PE and those who remained healthy during pregnancy, randomly selected from a prospective cohort. Overall, 23 miRNAs had a fold change > 2.0 and were considered to be upregulated in plasma from pregnant women who subsequently developed PE, even before the onset of clinical symptoms of PE. However, only miR-204-5p was statistically significant (P = 0.0082). Experimentally validated interactions for the target genes of miR-204-5p extracted from miRTarBase were used in the gene set functional enrichment analysis to identify Reactome pathways. The network connecting the 37 target genes for miR-204-5p revealed pathways of known pathophysiological relevance during the early development of PE and included key genes related to PE, such as BDNF, MMP-9, MALAT1, TGFBR2, and SIRT1. We further depicted downstream targets of SIRT1 that are related to the vascular endothelial function or implicated in the pathophysiology of PE, namely, FOXO1, NFκB, HIF-1α, NOS3, and PPAR-γ. Our novel findings provide for circulating miRNAs upregulated in the second trimester on plasma from pregnant women who subsequently developed PE that is potentially related to the early development of PE, which may guide further studies focused on the validation of potential predictive biomarkers in PE. Frontiers Media S.A. 2021-09-22 /pmc/articles/PMC8493119/ /pubmed/34630130 http://dx.doi.org/10.3389/fphys.2021.678184 Text en Copyright © 2021 Luizon, Conceição, Viana-Mattioli, Caldeira-Dias, Cavalli and Sandrim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Luizon, Marcelo R. Conceição, Izabela M. C. A. Viana-Mattioli, Sarah Caldeira-Dias, Mayara Cavalli, Ricardo C. Sandrim, Valeria C. Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p |
title | Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p |
title_full | Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p |
title_fullStr | Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p |
title_full_unstemmed | Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p |
title_short | Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p |
title_sort | circulating micrornas in the second trimester from pregnant women who subsequently developed preeclampsia: potential candidates as predictive biomarkers and pathway analysis for target genes of mir-204-5p |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493119/ https://www.ncbi.nlm.nih.gov/pubmed/34630130 http://dx.doi.org/10.3389/fphys.2021.678184 |
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