Genome-wide characterization of extrachromosomal circular DNA in breast cancer and its potential role in carcinogenesis and cancer progression
Zhimei Sheng,
Xuejie Wang,
Yuanhang Zheng,
Wanli Duan,
Jiayu Cui,
Lihui Gu,
Xinxin Gao,
Jing Ma,
Meimei Cui,
Hao Luo,
Wenhao Wang,
Lihong Shi,
Hongli Li,
Baogang Zhang
Affiliations
Zhimei Sheng
Department of Pathology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, China; Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China
Xuejie Wang
Department of Pathology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
Yuanhang Zheng
Department of Pathology, Weifang People’s Hospital, Weifang, Shandong, China
Wanli Duan
Medical Research Center, Shaoxing People’s Hospital, Shaoxing, Zhejiang, China
Jiayu Cui
Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China
Lihui Gu
Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China
Xinxin Gao
Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China
Jing Ma
Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China
Meimei Cui
Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China
Hao Luo
Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China
Wenhao Wang
Department of Medical Oncology, Affiliated Hospital of Shandong Second Medical University, Weifang, China
Lihong Shi
Department of Pharmacology, Shandong Second Medical University, Weifang, Shandong, China
Hongli Li
Department of Medicine Research Center, Shandong Second Medical University, Weifang, Shandong, China
Baogang Zhang
Department of Pathology, Shaoxing People’s Hospital, Shaoxing, Zhejiang, China; Corresponding author
Summary: 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.
