Evidence map›Paper›PMID 39614284›Full record

ArticleBiology direct2024

Integrating Circle-Seq with transcriptomics reveals genome-wide characterization of extrachromosomal circular DNA for dilated cardiomyopathy.

Zhenhao Lin, Fangjie Dai, Bo Li, Yongchao Zhao, Changqian Wang

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Article in Biology direct, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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6citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Zhenhao LinDepartment of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China.
Fangjie DaiDepartment of Cardiology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Bo LiDepartment of Radiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yongchao ZhaoDepartment of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563099, China. zhaoyc3988@126.com.
Changqian WangDepartment of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China. wangcq1218@sh9hospital.org.cn.

Funding

China National Postdoctoral Program for Innovative Talents BX20220094China Postdoctoral Science Foundation 2024M752030National Natural Science Foundation of China 82200290
6 · The paper itself

Abstract

backgroundExtrachromosomal circular DNAs (eccDNAs) are commonly found in various tumors and play a critical role in promoting oncogenesis. However, little is known about the characteristics and nature of eccDNAs in human heart failure. The aim of this study was to comprehensively analyze eccDNAs in human heart failure caused by dilated cardiomyopathy (DCM) and explore their potential functions.

methodsCircle-Seq and RNA-Seq were performed in cardiac tissue samples obtained from patients with DCM and healthy controls to identify eccDNAs and corresponding genes. Inward PCR, outward PCR and Sanger sequencing were conducted to validate the circular structure of eccDNAs. Bioinformatics was employed to probe the transcriptional activity of eccDNAs and their potential roles in the development of DCM. Ligase assisted minicircle accumulation strategy was used to synthesize a 500 bp circular DNA with a random sequence.

resultsEccDNAs originated from all chromosomes, with the majority being less than 1 kb in size and about half containing genes or gene fragments. They were derived from specific repeat elements and primarily mapped to 5'UTR, 3'UTR, and CpG islands. Gene-rich chromosomes 17 and 19 exhibited higher eccDNA enrichment. Sequence motifs flanking eccDNA junction sites displayed frequent nucleotide repeats. The circular structure of eccDNAs were confirmed. Integration of Circle-Seq and RNA-Seq data identified that large eccDNAs can be directly transcribed in non-dividing cardiomyocytes, indicating their potential roles in gene expression. Small circular DNA elicited a stronger cytokine response than linear DNA with the same sequence.

conclusionsOur work provided a detailed profiling of eccDNAs in both healthy and DCM hearts and demonstrated the potential functions of both large and small eccDNAs. These findings enhance the comprehension of the role of eccDNAs in cardiac pathophysiology and establish a theoretical foundation for future investigations on eccDNAs in DCM.

Indexed as

Cardiomyopathy, DilatedDNA, CircularHumansTranscriptomeDNA, CircularCircle-SeqDilated cardiomyopathyExtrachromosomal circular DNAHeart failureRNA-Seq

Identifiers

PMID39614284
PMCPMC11606223

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