Related Experiment Video
Updated: Oct 7, 2025
Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells
Published on: April 4, 2016
Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction
Huan Yang1,2,3,4, Jie He1,3,4, Shuai Huang1,3,4
1Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
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.
Insights
Extrachromosomal circular DNAs (eccDNAs) are more abundant in fetal growth restriction (FGR) placentas. These eccDNAs, originating from gene-rich regions, may offer new biomarkers and therapeutic targets for FGR.
Area of Science:
- Genomics
- Molecular Biology
- Pregnancy Research
Background:
- Extrachromosomal circular DNAs (eccDNAs) are found in normal and tumor cells, influencing gene expression and drug resistance.
- Fetal growth restriction (FGR) is a significant pregnancy complication with high infant morbidity and mortality.
- The role and characteristics of eccDNAs in FGR remain largely unexplored.
Purpose of the Study:
- To characterize the properties and potential functions of eccDNAs in FGR.
- To investigate the formation mechanisms and biological networks of eccDNAs in FGR placentas.
- To explore the utility of eccDNAs as potential biomarkers or therapeutic targets for FGR.
Main Methods:
- Circle-seq was employed to identify and profile eccDNAs in FGR and normal placental tissues.
- Bioinformatic analysis was used to analyze the expression profile of eccDNAs.
- Real-time PCR and Southern blot were utilized for verification of identified eccDNAs.
Main Results:
- A significant increase in eccDNA abundance was observed in FGR placentas compared to normal controls.
- Over 45,000 eccDNAs were identified, with specific length distributions (~146bp and ~340bp peaks).
- Host genes of differentially expressed eccDNAs were predominantly enriched in immune-related pathways, and associations with non-coding RNAs were noted.
Conclusions:
- This study provides the first comprehensive characterization of eccDNAs in FGR placentas.
- Identified eccDNAs and their associated mechanisms offer novel insights into FGR pathogenesis.
- EccDNAs represent promising candidates for developing new diagnostic biomarkers and therapeutic strategies for FGR.
