Work

Extrachromosomal circular DNA drives focal amplification of AGAP2-AS1 to promote cutaneous tumorigenesis

Year: 2026

Type: article

Abstract: Background: Extrachromosomal circular DNA (eccDNA) represents a pervasive structural continuum of genomic instability that drives intratumoral heterogeneity; the topography of the eccDNA-encoded non-coding transcriptome remains obscure in ultraviolet (UV)-driven malignancies. Methods: We profiled eccDNA from Basal Cell Carcinoma, Inverted Follicular Keratosis, Merkel Cell Carcinoma, and matched adjacent normal tissues using Circle-Seq. Structural data were integrated with the eccDNA Gene Analyzer (ECGA) and The Cancer Genome Atlas (TCGA) clinical cohorts. In vitro siRNA-mediated knockdown assays were used to determine the oncogenic functionality of identified lncRNAs. Results: Circle-Seq revealed genome-wide remodeling of circular DNA with focal hyper-amplification, GC-rich compositional biases, and recurrent hotspots on chromosomes 9, 16, and 20. Integrative screening identified AGAP2-AS1 as a clinically significant, copy-number-associated lncRNA, whose expression correlated with cellular responses to UV radiation and oxidative stress. Depletion of AGAP2-AS1 impaired tumor cell proliferation, migration, and invasion in vitro. Conclusion: The eccDNA landscape serves as a reservoir of functional non-coding elements; focal amplification of AGAP2-AS1 contributes to malignant progression and stress adaptation in cutaneous neoplasia.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1906797