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

作者：Huan Yang, Jie He, Shuai Huang, Hongbing Yang, Qingjie Yi, Yuelan Tao, Miaomiao Chen, Xuemei Zhang, Hongbo Qi · 发表于：Frontiers in Immunology · 年份：2021 · DOI：10.3389/fimmu.2021.780779 · 被引用次数：26 · 研究领域：Cancer-related molecular mechanisms research、Cancer Genomics and Diagnostics、Prenatal Screening and Diagnostics

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 ...