染色体外环状 DNA (eccDNA) 被定义为环状和移动 DNA 分子的独特基因组实体，但它们在乳腺癌 (BC) 中的分子功能和影响却鲜为人知。本研究使用 Circle-seq 分析了 19 个 BC 组织和 17 个邻近正常组织的 eccDNA。我们发现 eccDNA 存在于所有染色体上，并富含与 BC 途径相关的七个 eccDNA 热点基因 (HSG)。几个包含完整基因 (eccGenes) 的 eccDNA 和包含 miRNA (eccMIR) 的 eccDNA 已被鉴定并与癌症相关通路相关联。合成的 eccMIR6748、eccMIR6508 和 eccMIR3142 提高了 MCF-7 细胞中的 miRNA 表达，其中 eccMIR6748 通过上调 miR-6748 促进 BC 细胞迁移和侵袭，而 miR-6748 在转录后水平抑制肿瘤抑制候选因子 5 (TUSC5)。 eccMIR6748 还通过 p38 丝裂原激活蛋白激酶 (MAPK) 信号通路影响 BC 进展。这些发现表明，含有功能基因组片段的 eccDNA 在 BC 的起始和进展中发挥作用，提供了基因组可塑性的动态来源以及作为生物标志物和治疗靶点的潜力。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Extrachromosomal circular DNAs (eccDNAs) are defined as distinct genomic entities of circular and mobile DNA molecules, but their molecular functions in and impact on breast cancer (BC) are rarely known. This study used Circle-seq to analyze eccDNAs from 19 BC tissues and 17 adjacent normal tissues. We found that eccDNAs are present on all chromosomes and enriched in seven eccDNA hotspot genes (HSGs) associated with the BC pathway. Several eccDNAs harboring entire genes (eccGenes) and eccDNAs harboring miRNAs (eccMIRs) were identified and linked to cancer-relevant pathways. Synthetic eccMIR6748, eccMIR6508, and eccMIR3142 elevated miRNA expression in MCF-7 cells, with eccMIR6748 promoting BC cell migration and invasion by upregulating miR-6748, which suppresses tumor suppressor candidate factor 5 (TUSC5) at the post-transcriptional level. eccMIR6748 also influences BC progression via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. These findings suggest that eccDNAs, which contain functional genomic segments, play a role in BC initiation and progression, offering a dynamic source of genomic plasticity and potential as biomarkers and therapeutic targets.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.