染色体外DNA
癌变
乳腺癌
癌症
基因组
生物
DNA
遗传学
癌症研究
计算生物学
基因
作者
Zhimei Sheng,Xuejie Wang,Yuanhang Zheng,Wanli Duan,Jiayu Cui,Lihui Gu,Xinxin Gao,Jing Wang,Meimei Cui,Hao Luo,Wenhao Wang,Lihong Shi,Hongli Li,Baogang Zhang
出处
期刊:Cell Reports
[Elsevier]
日期:2024-10-16
卷期号:43 (11): 114845-114845
标识
DOI:10.1016/j.celrep.2024.114845
摘要
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.
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