Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Huan Yang; Huan Yang; Huan Yang; Huan Yang; Jie He; Jie He; Jie He; Shuai Huang; Shuai Huang; Shuai Huang; Hongbing Yang; Qingjie Yi; Qingjie Yi; Yuelan Tao; Yuelan Tao; Yuelan Tao; Miaomiao Chen; Miaomiao Chen; Miaomiao Chen; Xuemei Zhang; Xuemei Zhang; Xuemei Zhang; Hongbo Qi; Hongbo Qi; Hongbo Qi

doi:10.3389/fimmu.2021.780779

Frontiers in Immunology (Dec 2021)

Identification and Characterization of Extrachromosomal Circular DNA in Human Placentas With Fetal Growth Restriction

Huan Yang,
Huan Yang,
Huan Yang,
Huan Yang,
Jie He,
Jie He,
Jie He,
Shuai Huang,
Shuai Huang,
Shuai Huang,
Hongbing Yang,
Qingjie Yi,
Qingjie Yi,
Yuelan Tao,
Yuelan Tao,
Yuelan Tao,
Miaomiao Chen,
Miaomiao Chen,
Miaomiao Chen,
Xuemei Zhang,
Xuemei Zhang,
Xuemei Zhang,
Hongbo Qi,
Hongbo Qi,
Hongbo Qi

Affiliations

Huan Yang: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Huan Yang: Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing, China
Huan Yang: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Huan Yang: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
Jie He: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Jie He: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Jie He: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
Shuai Huang: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Shuai Huang: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Shuai Huang: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
Hongbing Yang: Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing, China
Qingjie Yi: Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing, China
Qingjie Yi: Department of Epidemiology and Health Statistics, School of Public Health and Management, Chongqing Medical University, Chongqing, China
Yuelan Tao: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Yuelan Tao: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Yuelan Tao: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
Miaomiao Chen: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Miaomiao Chen: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Miaomiao Chen: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
Xuemei Zhang: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Xuemei Zhang: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Xuemei Zhang: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
Hongbo Qi: Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Hongbo Qi: Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
Hongbo Qi: China-Canada-New Zealand Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China

DOI: https://doi.org/10.3389/fimmu.2021.780779
Journal volume & issue: Vol. 12

Abstract

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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.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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