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Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction
Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724250/ https://www.ncbi.nlm.nih.gov/pubmed/34992600 http://dx.doi.org/10.3389/fimmu.2021.780779 |
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author | Yang, Huan He, Jie Huang, Shuai Yang, Hongbing Yi, Qingjie Tao, Yuelan Chen, Miaomiao Zhang, Xuemei Qi, Hongbo |
author_facet | Yang, Huan He, Jie Huang, Shuai Yang, Hongbing Yi, Qingjie Tao, Yuelan Chen, Miaomiao Zhang, Xuemei Qi, Hongbo |
author_sort | Yang, Huan |
collection | PubMed |
description | Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from the fetus. Fetal growth restriction (FGR) is a pregnancy-related disease associated with high newborn morbidity and mortality. However, the characteristics and nature of eccDNAs/ecDNAs in FGR are poorly understood. This study aims to deconstruct the properties and potential functions of eccDNAs/ecDNAs in FGR. We performed circle-seq to identify the expression profile of eccDNAs/ecDNAs, analyzed by bioinformatics, and verified by real-time Polymerase Chain Reaction (PCR) combined with southern blot in FGR compared with the normal groups. A total of 45,131 eccDNAs/ecDNAs (including 2,118 unique ones) were identified, which had significantly higher abundance in FRG group than in normal group, and was bimodal in length, peaking at ~146bp and ~340bp, respectively. Gestational age may be one independent factor affecting the production of eccDNAs/ecDNAs, most of which come from genomic regions with high gene density, with a 4~12bp repeat around the junction, and their origin had a certain genetic preference. In addition, some of the host-genes overlapped with non-coding RNAs (ncRNAs) partially or even completely. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that host-genes on the differentially expressed eccDNAs/ecDNAs (DEEECs/DEECs) were mainly enriched in immune-related functions and pathways. The presence of some ecDNAs were verified, and whose variability were consistent with the circle-seq results. We identified and characterized eccDNAs/ecDNAs in placentas with FGR, and elucidated the formation mechanisms and the networks with ncRNAs, which provide a new vision for the screening of new biomarkers and therapeutic targets for FGR. |
format | Online Article Text |
id | pubmed-8724250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87242502022-01-05 Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction Yang, Huan He, Jie Huang, Shuai Yang, Hongbing Yi, Qingjie Tao, Yuelan Chen, Miaomiao Zhang, Xuemei Qi, Hongbo Front Immunol Immunology Many studies have confirmed that extrachromosomal circular DNAs (eccDNAs/ecDNAs) exist in tumor and normal cells independently of the chromosome and are essential for oncogene plasticity and drug resistance. Studies have confirmed that there are many eccDNAs/ecDNAs in maternal plasma derived from the fetus. Fetal growth restriction (FGR) is a pregnancy-related disease associated with high newborn morbidity and mortality. However, the characteristics and nature of eccDNAs/ecDNAs in FGR are poorly understood. This study aims to deconstruct the properties and potential functions of eccDNAs/ecDNAs in FGR. We performed circle-seq to identify the expression profile of eccDNAs/ecDNAs, analyzed by bioinformatics, and verified by real-time Polymerase Chain Reaction (PCR) combined with southern blot in FGR compared with the normal groups. A total of 45,131 eccDNAs/ecDNAs (including 2,118 unique ones) were identified, which had significantly higher abundance in FRG group than in normal group, and was bimodal in length, peaking at ~146bp and ~340bp, respectively. Gestational age may be one independent factor affecting the production of eccDNAs/ecDNAs, most of which come from genomic regions with high gene density, with a 4~12bp repeat around the junction, and their origin had a certain genetic preference. In addition, some of the host-genes overlapped with non-coding RNAs (ncRNAs) partially or even completely. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that host-genes on the differentially expressed eccDNAs/ecDNAs (DEEECs/DEECs) were mainly enriched in immune-related functions and pathways. The presence of some ecDNAs were verified, and whose variability were consistent with the circle-seq results. We identified and characterized eccDNAs/ecDNAs in placentas with FGR, and elucidated the formation mechanisms and the networks with ncRNAs, which provide a new vision for the screening of new biomarkers and therapeutic targets for FGR. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724250/ /pubmed/34992600 http://dx.doi.org/10.3389/fimmu.2021.780779 Text en Copyright © 2021 Yang, He, Huang, Yang, Yi, Tao, Chen, Zhang and Qi 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 | Immunology Yang, Huan He, Jie Huang, Shuai Yang, Hongbing Yi, Qingjie Tao, Yuelan Chen, Miaomiao Zhang, Xuemei Qi, Hongbo Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction |
title | Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction |
title_full | Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction |
title_fullStr | Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction |
title_full_unstemmed | Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction |
title_short | Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction |
title_sort | identification and characterization of extrachromosomal circular dna in human placentas with fetal growth restriction |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724250/ https://www.ncbi.nlm.nih.gov/pubmed/34992600 http://dx.doi.org/10.3389/fimmu.2021.780779 |
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