{
  "abstract": "Chemoresistance remains a major obstacle to effective treatment of non-small cell lung cancer (NSCLC), yet the epigenetic mechanisms underlying platinum resistance remain incompletely understood. Here, we show that Jumonji C domain-containing protein 5 (JMJD5) promotes platinum resistance in NSCLC cells and xenograft tumors while inducing a slow-proliferative, mesenchymal-like phenotype characterized by enhanced migration, invasion, spheroid formation, and epithelial-mesenchymal transition (EMT). Mechanistically, JMJD5 interacted with RCC1 domain-containing protein 1 (RCCD1), and cisplatin treatment promoted their nuclear accumulation concomitant with reduced H3K36me2 levels. RCCD1 depletion attenuated JMJD5-associated H3K36me2 demethylation and reversed EMT-associated phenotypes and cisplatin resistance, supporting RCCD1 as a functional cofactor of JMJD5-mediated chromatin remodeling. Fibronectin 1 (FN1) was further identified as a downstream effector of this pathway. Genetic or pharmacological inhibition of FN1 suppressed JMJD5-induced migration and invasion and restored cisplatin sensitivity. Notably, JMJD5-dependent FN1 protein accumulation required ongoing protein synthesis without a corresponding increase in FN1 mRNA, suggesting post-transcriptional regulation. Consistently, elevated FN1 expression was associated with unfavorable overall survival in patients with lung cancer. Collectively, these findings reveal a JMJD5-RCCD1-H3K36me2-FN1 regulatory axis linking chemotherapy-induced epigenetic remodeling to EMT-associated platinum resistance and suggest that disruption of this pathway may represent a potential strategy for overcoming chemoresistance in NSCLC.",
  "abstract_shown": true,
  "affiliations": [
    "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.",
    "Postgraduate·Training Base Alliance of Wenzhou Medical University·(Zhejiang Cancer Hospital), Hangzhou, 310022, Zhejiang, China.",
    "Department of Pathology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China. xiangxueping@zju.edu.cn.",
    "Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China. fangluo@zjcc.org.cn.",
    "Postgraduate·Training Base Alliance of Wenzhou Medical University·(Zhejiang Cancer Hospital), Hangzhou, 310022, Zhejiang, China. fangluo@zjcc.org.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lili Tan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinghui Tong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wanying Zhou"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinyue Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Qilu Fang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Feng"
    },
    {
      "affs": [
        2
      ],
      "name": "Xueping Xiang"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Luo Fang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dey29yavrzkpp.bib",
  "cited_by": 0,
  "doi": "10.1186/s43556-026-00625-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13687518",
  "id": "dey29yavrzkpp",
  "issns": [
    "2662-8651"
  ],
  "landing_url": "https://europepmc.org/article/MED/42905309",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7223123799",
  "pdf_url": "https://europepmc.org/articles/PMC13687518?pdf=render",
  "pmcid": "PMC13687518",
  "pmid": "42905309",
  "published": "2026-10-21",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/dey29yavrzkpp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42905309",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42905309"
    },
    {
      "first_seen": "2026-10-30T13:45:39Z",
      "native_id": "db169d94427142dbbfe78268a61bebc3",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s43556-026-00625-y"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "RCCD1-JMJD5 coordinate histone demethylation to promote platinum resistance in non-small cell lung cancer via FN1-mediated epithelial-mesenchymal transition.",
  "title_text": "RCCD1-JMJD5 coordinate histone demethylation to promote platinum resistance in non-small cell lung cancer via FN1-mediated epithelial-mesenchymal transition.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:39Z",
  "url": "https://research.draconitic.com/paper/dey29yavrzkpp",
  "venue": "Molecular biomedicine",
  "versions": []
}