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Extrachromosomal circular MiR-17-92 amplicon promotes HCC

Sailan Zou1, Shihan Chen1, Guocheng Rao1

  • 1Department of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China.

Hepatology (Baltimore, Md.)
|May 1, 2023
PubMed
Abstract

Insights

Extrachromosomal circular DNAs (eccDNAs) are abundant in liver cancer (HCC) and drive tumor growth. This study characterizes HCC eccDNAs, revealing microRNA-17-92 containing eccDNAs promote HCC progression.

Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Extrachromosomal circular DNAs (eccDNAs) are recognized as significant oncogenic drivers in cancer genomes.
  • The specific role, structure, and prevalence of eccDNAs in hepatocellular carcinoma (HCC), a leading cause of cancer mortality, remain largely uninvestigated.

Purpose of the Study:

  • To comprehensively characterize eccDNAs in human HCC.
  • To elucidate the oncogenic function of microRNA (miRNA)-17-92-containing eccDNAs in HCC tumor progression.

Main Methods:

  • Circle-sequencing to identify and quantify eccDNAs from HCC and adjacent non-tumor tissues.
  • Outward PCR and Sanger sequencing for eccDNA validation.
  • Quantitative PCR to assess miRNA and eccDNA levels.
  • Functional assays using artificial DNA circles with the miR-17-92 cluster.

Main Results:

  • Over 230,000 eccDNAs were identified, showing enrichment in HCC tumors and specific chromosomal origins.
  • eccDNAs containing the miRNA-17-92 cluster were validated and found to be elevated in HCC.
  • Elevated miRNA-17-92 eccDNAs correlated with poor patient outcomes and advanced age.
  • Exogenous expression of miR-17-92 eccDNAs accelerated HCC cell proliferation and migration.

Conclusions:

  • This study provides the first genome-wide eccDNA profile for HCC.
  • Highlights the functional importance of miRNA-containing eccDNAs in HCC tumorigenesis.
  • Offers novel insights into HCC pathogenesis, potential therapeutic targets, and eccDNA/miRNA biology.

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