Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype
Megabase-sized extrachromosomal circular DNA with intact oncogenes (ecDNA) plays crucial roles in cancer. However, the impact of smaller (100 bp-1 Mb), more ubiquitous extrachromosomal circular DNA (eccDNA) on tumor pathology is unclear. We analyze eccDNA from 122 renal tumors and adjacent tissues, finding increased eccDNA in late-stage cancers, correlating with heightened patient mortality and copy-number amplification. Large eccDNAs are rare, and smaller eccDNAs predominate. The microRNA (miRNA) genes MIR107, MIR196a, MIR495, and MIR519 are recurrently found on eccDNA, almost exclusively in tumors, and patients with any one of these exhibited shorter progression-free survival. Synthetic eccDNAs with these MIR genes increase cancer cell proliferation in 786-O cells, suggesting oncogenic potential. Additionally, we found eccDNA carrying full protein-coding genes that are overexpressed in transcriptional analyses. Our findings suggest that small eccDNAs with miRNA genes are functional and contribute to the tumorigenesis of renal cell carcinoma.
Authors
- Yuchen Zeng (ORCID: https://orcid.org/0000-0001-5873-5948)
- Jan Gorodkin (ORCID: https://orcid.org/0000-0001-5823-4000)
- Huanming Yang (ORCID: https://orcid.org/0000-0002-0858-3410)
- Peng Han (ORCID: https://orcid.org/0000-0002-3405-087X)
- Xi Xiang (ORCID: https://orcid.org/0000-0002-5590-7289)
- Jakob H. Havgaard (ORCID: https://orcid.org/0000-0002-4816-814X)
- Huiying Tao
- Xiaolong Sui (ORCID: https://orcid.org/0000-0001-7004-1973)
- Xiaoguang Pan (ORCID: https://orcid.org/0000-0002-2688-9245)
- Birgitte Regenberg (ORCID: https://orcid.org/0000-0003-4996-7012)
- Xue Liang (ORCID: https://orcid.org/0000-0001-6864-7386)
- Chunhua Lin (ORCID: https://orcid.org/0000-0001-5225-3518)
- Wenting Wang (ORCID: https://orcid.org/0000-0002-8344-0102)
- Shan Gao (ORCID: https://orcid.org/0009-0002-1705-8033)
- Wei Dong (ORCID: https://orcid.org/0000-0001-6386-0831)
- Tianxi Yu (ORCID: https://orcid.org/0009-0007-2335-2964)
- Zhe Xu (ORCID: https://orcid.org/0000-0001-6789-5214)
- Wei Lv (ORCID: https://orcid.org/0000-0001-6037-8759)
- Shuang Wu (ORCID: https://orcid.org/0009-0006-2296-7273)
Institutions
- Qingdao University (CN)
- University of Copenhagen (DK)
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Yuhuangding Hospital (CN)
- The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
- Affiliated Hospital of Qingdao University (CN)
- Qingdao Huanghai University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116660
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94