Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype

Peng Han; Wei Lv; Zhe Xu; Tianxi Yu; Shan Gao; Xi Xiang; Xiaoguang Pan; Yuchen Zeng; Jakob Hull Havgaard; Jan Gorodkin; Xue Liang; Shuang Wu; Huiying Tao; Xiaolong Sui; Wenting Wang; Wei Dong; Huanming Yang; Chunhua Lin; Birgitte Regenberg

doi:10.1016/j.celrep.2025.116660

Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype

Peng Han
, Wei Lv
, Zhe Xu
, Tianxi Yu
, Shan Gao
, Xi Xiang
, Xiaoguang Pan
, Yuchen Zeng
, Jakob Hull Havgaard
, Jan Gorodkin
, Xue Liang
, Shuang Wu
, Huiying Tao
, Xiaolong Sui
, Wenting Wang
, Wei Dong
, Huanming Yang
, Chunhua Lin
, Birgitte Regenberg

The Seventh Affiliated Hospital Sun Yat-sen University
Chinese Academy of Sciences
Qingdao University
Yantai Yuhuangding Hospital
Hongshiya Community Healthcare Center
University of Copenhagen

科研成果: 期刊稿件 › 文章 › 同行评审

3 引用（Scopus）

摘要

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.

源语言	英语
页（从-至）	116660
页数	1
期刊	Cell Reports
卷	44
期	12
DOI	https://doi.org/10.1016/j.celrep.2025.116660
出版状态	已出版 - 23 12月 2025
已对外发布	是

联合国可持续发展目标

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可持续发展目标 3 良好健康与福祉

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10.1016/j.celrep.2025.116660

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引用此

Han, P., Lv, W., Xu, Z., Yu, T., Gao, S., Xiang, X., Pan, X., Zeng, Y., Havgaard, J. H., Gorodkin, J., Liang, X., Wu, S., Tao, H., Sui, X., Wang, W., Dong, W., Yang, H., Lin, C., & Regenberg, B. (2025). Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype. Cell Reports, 44(12), 116660. https://doi.org/10.1016/j.celrep.2025.116660

@article{aedb99bd07864d638547337818603b16,

title = "Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype",

abstract = "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.",

keywords = "CP: cancer, double minutes, ecDNA, eccDNA, extrachromosomal circular DNA, renal cell carcinoma",

author = "Peng Han and Wei Lv and Zhe Xu and Tianxi Yu and Shan Gao and Xi Xiang and Xiaoguang Pan and Yuchen Zeng and Havgaard, \{Jakob Hull\} and Jan Gorodkin and Xue Liang and Shuang Wu and Huiying Tao and Xiaolong Sui and Wenting Wang and Wei Dong and Huanming Yang and Chunhua Lin and Birgitte Regenberg",

note = "Publisher Copyright: Copyright {\textcopyright} 2025. Published by Elsevier Inc.",

year = "2025",

month = dec,

day = "23",

doi = "10.1016/j.celrep.2025.116660",

language = "英语",

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pages = "116660",

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TY - JOUR

T1 - Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype

AU - Han, Peng

AU - Lv, Wei

AU - Xu, Zhe

AU - Yu, Tianxi

AU - Gao, Shan

AU - Xiang, Xi

AU - Pan, Xiaoguang

AU - Zeng, Yuchen

AU - Havgaard, Jakob Hull

AU - Gorodkin, Jan

AU - Liang, Xue

AU - Wu, Shuang

AU - Tao, Huiying

AU - Sui, Xiaolong

AU - Wang, Wenting

AU - Dong, Wei

AU - Yang, Huanming

AU - Lin, Chunhua

AU - Regenberg, Birgitte

PY - 2025/12/23

Y1 - 2025/12/23

N2 - 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.

AB - 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.

KW - CP: cancer

KW - double minutes

KW - ecDNA

KW - eccDNA

KW - extrachromosomal circular DNA

KW - renal cell carcinoma

UR - https://www.scopus.com/pages/publications/105026348305

U2 - 10.1016/j.celrep.2025.116660

DO - 10.1016/j.celrep.2025.116660

M3 - 文章

C2 - 41379614

AN - SCOPUS:105026348305

SN - 2211-1247

VL - 44

SP - 116660

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -

Extrachromosomal circular miRNA-gene amplifications contribute to the renal cancer phenotype

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