{
  "abstract": "Objectives: Circular RNAs (circRNAs) can encode functional peptides to regulate tumor progression, yet the roles of circRNA-encoded peptides in epithelial ovarian cancer (EOC) remain poorly understood. This study aimed to investigate the function of hsa_circ_0000615 (circ_0615) and its encoded polypeptide in EOC and explore its potential pre-clinical value as a candidate therapeutic target. Methods: We detected circ_0615 expression in EOC clinical tissues and cell lines. In vitro functional assays, in vivo xenograft and Patient-derived xenograft (PDX) models with adeno-associated virus (AAV)-mediated overexpression were used to assess tumor-suppressive phenotypes. Mass spectrometry, co-immunoprecipitation, western blotting, immunofluorescence, and chromatin immunoprecipitation were applied to characterize the circ_0615-encoded polypeptide Zinc Finger Protein 609-250-amino acid (ZNF609-250aa) and its interaction with high-mobility group box 1 (HMGB1). Results: circ_0615 was downregulated in EOC tissues and cell lines. Circ_0615 overexpression suppressed EOC proliferation and migration in vitro and in vivo. Mechanistically, circ_0615 promoted translation of ZNF609-250aa via eukaryotic translation initiation factor 2 subunit 1 (eIF2α). ZNF609-250aa bound HMGB1, reduced its ubiquitination, and promoted HMGB1 nuclear accumulation, which may contribute to repression of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) transcription. AAV2/8-ZNF609-250aa restrained tumor growth in PDX models. Conclusion: Circ_0615-encoded ZNF609-250aa acts as a tumor suppressor in EOC, partially through modulating ZNF609-250aa-HMGB1-related molecular events. This study provides novel mechanistic insights and promising pre-clinical candidate targets requiring further validation for EOC intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China",
    "Department of Integration of Western and Traditional Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China",
    "Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China",
    "Department of Pathology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China",
    "Gynecology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China",
    "Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China",
    "Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Shanghai, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ziyi Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Siyun Deng"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiao Meng"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaofei Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yueyou Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Jiami Huang"
    },
    {
      "affs": [
        4
      ],
      "name": "Tonglu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Min Liu"
    },
    {
      "affs": [
        5
      ],
      "name": "Henghui Yang"
    },
    {
      "affs": [
        5
      ],
      "name": "Fangzhou Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Wang"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Wei Meng"
    },
    {
      "affs": [
        5
      ],
      "name": "Shaojia Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanli Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6fqneztc25yd5.bib",
  "cited_by": 0,
  "doi": "10.32604/or.2026.087931",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732393/",
  "id": "6fqneztc25yd5",
  "issns": [
    "0965-0407",
    "1555-3906"
  ],
  "landing_url": "https://doi.org/10.32604/or.2026.087931",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Circular RNAs in diseases"
    ]
  ],
  "openalex": "W7221078364",
  "pdf_url": "https://www.techscience.com/files/onlinefirst/2026/10.9/TSP_OR_87931/TSP_OR_87931.pdf",
  "pmcid": "PMC13732393",
  "pmid": "42984912",
  "published": "2026-10-28",
  "publisher": "Tech Science Press",
  "ris": "https://research.draconitic.com/paper/6fqneztc25yd5.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:23Z",
      "native_id": "PMC13732393",
      "source": "pmc",
      "url": "https://doi.org/10.32604/or.2026.087931"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Circular RNAs in diseases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Hsa_Circ_0000615-Encoded 250-Amino Acid Polypeptide Suppresses Epithelial Ovarian Cancer Progression via Promoting HMGB1 Nuclear Accumulation",
  "title_text": "Hsa_Circ_0000615-Encoded 250-Amino Acid Polypeptide Suppresses Epithelial Ovarian Cancer Progression via Promoting HMGB1 Nuclear Accumulation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:23Z",
  "url": "https://research.draconitic.com/paper/6fqneztc25yd5",
  "venue": "Oncology Research",
  "versions": []
}