Project description:Cell-free extrachromosomal circular DNA (eccDNA) as a distinct topological form from linear DNA has recently gained increasing research interest, with possible clinical applications as a class of biomarkers. In this study, we aimed to explore the relationship between nucleases and eccDNA characteristics in plasma. By using knockout mouse models with deficiencies in deoxyribonuclease 1 (DNASE1) or deoxyribonuclease 1 like 3 (DNASE1L3), we found that cell-free eccDNA in Dnase1l3-/- mice exhibited larger size distributions than that in wild-type mice. Such size alterations were not found in tissue eccDNA of either Dnase1-/- or Dnase1l3-/- mice, suggesting that DNASE1L3 could digest eccDNA extracellularly but did not seem to affect intracellular eccDNA. Using a mouse pregnancy model, we observed that in Dnase1l3-/- mice pregnant with Dnase1l3+/- fetuses, the eccDNA in the maternal plasma was shorter compared with that of Dnase1l3-/- mice carrying Dnase1l3-/- fetuses, highlighting the systemic effects of circulating fetal DNASE1L3 degrading the maternal eccDNA extracellularly. Furthermore, plasma eccDNA in patients with DNASE1L3 mutations also exhibited longer size distributions than that in healthy controls. Taken together, this study provided a hitherto missing link between nuclease activity and the biological manifestations of eccDNA in plasma, paving the way for future biomarker development of this special form of DNA molecules.

| S-EPMC9089787 | biostudies-literature

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

Project description:Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. We combined Circle-Seq and RNA-Seq to identified crucial extrachromosomal circular oncogene amplicons. Herein, we revealed that extrachromosomal circular SUZ12 amplicon regulates H3K27me3 modification during the oncogenic progression of retinoblastoma. Conclusively, our study initially delineated an integrated picture of the eccDNA landscape in retinoblastoma and unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

2023-07-02 | GSE235888 | GEO

The Adaptational Dynamics of Extrachromosomal Circular DNA in Rice

Project description:The Adaptational Dynamics of Extrachromosomal Circular DNA in Rice

| PRJEB59090 | ENA

Pathways for macrophage uptake of cell-free circular RNAs

Project description:Circular RNAs (CircRNAs) are stable RNAs present in cell-free RNA, comprising cellular debris and pathogen genomes. As a prerequisite for the development of efficient circRNA-based therapies, we investigated the phenomenon and mechanism of cellular uptake and intracellular fate of circRNAs. Human myeloid cells and B cells selectively internalize extracellular circRNAs. Macrophage uptake of circRNA is rapid, energy-dependent, and saturable. CircRNA uptake can lead to translation of encoded sequences and antigen presentation. The route of internalization influences immune activation after circRNA uptake, with distinct gene expression programs depending on the mechanism involved. Genome-scale CRISPR screens and chemical inhibitor studies nominate macrophage scavenger receptor MSR1, toll-like receptors, and mTOR signaling as key regulators of receptor-mediated phagocytosis of circRNAs, a dominant pathway to internalize circRNAs in parallel to macropinocytosis. These results suggest that cell-free circRNA serves as an "eat me" signal and a danger-associated molecular pattern, indicating orderly pathways of recognition and disposal.

2024-08-01 | GSE264160 | GEO

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas

Project description:Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas

| PRJNA1005992 | ENA

Engineered extrachromosomal circular DNAs promote tumorigenesis (WGS)

Project description:Engineered extrachromosomal circular DNAs promote tumorigenesis (WGS)

| PRJNA1100545 | ENA