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

Peng Han1, Wei Lv2, Zhe Xu3

  • 1Scientific Research Center, Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

Cell Reports
|December 11, 2025
PubMed

Insights

Smaller extrachromosomal circular DNA (eccDNA) is more common in late-stage kidney cancer, linked to worse survival. Specific microRNA genes on eccDNA promote cancer cell growth, suggesting a role in tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Extrachromosomal circular DNA (ecDNA) is implicated in cancer, but the role of smaller, more abundant eccDNA is unknown.
  • Renal cell carcinoma (RCC) is a significant health concern, necessitating further understanding of its molecular underpinnings.

Purpose of the Study:

  • To investigate the role of small eccDNA in renal tumors.
  • To determine the association between eccDNA and RCC progression and patient outcomes.

Main Methods:

  • Analysis of eccDNA from 122 renal tumors and adjacent tissues.
  • Correlation analysis of eccDNA levels with cancer stage, patient mortality, and copy-number amplification.
  • Identification and functional assessment of miRNA genes on eccDNA.

Main Results:

  • Increased eccDNA abundance in late-stage RCC, correlating with poorer survival and copy-number amplification.
  • Recurrent presence of specific miRNA genes (MIR107, MIR196a, MIR495, MIR519) on tumor eccDNA, associated with shorter progression-free survival.
  • Synthetic eccDNAs carrying these miRNA genes enhanced proliferation in RCC cells, indicating oncogenic potential.

Conclusions:

  • Small eccDNAs, particularly those harboring miRNA genes, are functional and contribute to renal cell carcinoma tumorigenesis.
  • eccDNA represents a potential therapeutic target and biomarker in RCC.
Keywords:
CP: cancerdouble minutesecDNAeccDNAextrachromosomal circular DNArenal cell carcinoma

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