{
  "abstract": "Background: Gestational choriocarcinoma is an aggressive gynecologic malignancy that can occur with various pregnancy events. Although typically highly sensitive to combination chemotherapy, this malignancy, in a subset of patients, develops resistance to etoposide-containing regimens, leading to therapeutic failure. We aimed to elucidate the molecular mechanisms that confer resistance to etoposide, a central component of choriocarcinoma chemotherapy.\n\nMethods: Etoposide-resistant JAR and JEG-3 choriocarcinoma cell lines were established by continuous stepwise exposure of parental cells to increasing concentrations of etoposide. Phenotypic comparisons with the parental cells were then performed. RNA sequencing and upstream regulator analyses were conducted to identify key regulatory molecules and signaling pathways associated with etoposide resistance. Candidate molecules were further evaluated by siRNA-mediated knockdown to assess their effects on etoposide sensitivity.\n\nResults: Compared with their parental cells, etoposide-resistant choriocarcinoma cells demonstrated significantly reduced proliferation (p < 0.001), migration (p < 0.05), and invasion (p < 0.01). RNA sequencing and pathway analyses revealed suppression of pathways related to cell cycle progression and DNA replication. In addition, upstream regulator analysis focusing on kinases suggested the involvement of MAPK-related molecules, including MAPK9, MAP2K5, and MAPK7. siRNA-mediated suppression of MAPK7 in resistant cells restored sensitivity to etoposide, suggesting a role for MAPK7 in the maintenance of etoposide resistance.\n\nConclusion: Our findings indicate that the MAPK signaling pathway, particularly MAPK7, contributes to etoposide resistance in choriocarcinoma, based on RNA sequencing and functional analyses of resistant cell models.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16640-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsuruma-Cho 65, Showa-Ku, Nagoya, 466-8550 Japan",
    "Department of Obstetrics and Gynecology, Aichi Medical University School of Medicine, Nagakute, Japan",
    "Institute for Advanced Research, Nagoya University, Nagoya, Japan",
    "Laboratory of Integrative Oncology, National Cancer Center Research Institute, Tokyo, Japan",
    "Department of Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan",
    "Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuko Yasui"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Kosuke Yoshida",
      "orcid": "0000-0003-1484-4872"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuki Nishiko"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Hironori Suzuki"
    },
    {
      "affs": [
        3
      ],
      "name": "Yusuke Yamamoto"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Kazumasa Mogi"
    },
    {
      "affs": [
        0
      ],
      "name": "Masato Yoshihara"
    },
    {
      "affs": [
        0
      ],
      "name": "Yukari Nagao"
    },
    {
      "affs": [
        0
      ],
      "name": "Satoshi Tamauchi"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Akira Yokoi"
    },
    {
      "affs": [
        0
      ],
      "name": "Nobuhisa Yoshikawa"
    },
    {
      "affs": [
        5
      ],
      "name": "Kimihiro Nishino"
    },
    {
      "affs": [
        5
      ],
      "name": "Eiko Yamamoto"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaoru Niimi",
      "orcid": "0000-0003-4546-9606"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiroaki Kajiyama"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b7zky08hqtd0k.bib",
  "cited_by": 0,
  "doi": "10.1186/s12885-026-16640-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711928/",
  "id": "b7zky08hqtd0k",
  "issns": [
    "1471-2407"
  ],
  "landing_url": "https://doi.org/10.1186/s12885-026-16640-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2739|Gestational Trophoblastic Disease Studies"
    ]
  ],
  "openalex": "W7171947696",
  "pdf_url": null,
  "pmcid": "PMC13711928",
  "pmid": "42947026",
  "published": "2026-07-31",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/b7zky08hqtd0k.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:37Z",
      "native_id": "PMC13711928",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12885-026-16640-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Gestational Trophoblastic Disease Studies",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Characterization of etoposide-resistant choriocarcinoma cells and contribution of MAPK7 to etoposide resistance",
  "title_text": "Characterization of etoposide-resistant choriocarcinoma cells and contribution of MAPK7 to etoposide resistance",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:37Z",
  "url": "https://research.draconitic.com/paper/b7zky08hqtd0k",
  "venue": "BMC Cancer",
  "versions": []
}