{
  "abstract": "Background\n\nSorafenib exerts antitumor activity in clear cell renal cell carcinoma (ccRCC), but its precise mechanisms involving regulated cell death remain incompletely understood. Ferroptosis has emerged as an important effector of sorafenib-mediated antitumor activity; however, the regulatory network controlling ferroptosis in ccRCC, particularly the role of epitranscriptomic regulators such as the N6-methyladenosine reader YTHDF1, remains poorly defined.Results\n\nSorafenib induced ferroptosis in ccRCC cells, as evidenced by increased intracellular ferrous iron, reactive oxygen species, lipid peroxides, and malondialdehyde levels, and was accompanied by reduced YTHDF1 expression. Genetic silencing of YTHDF1 robustly activated both ferroptosis and apoptosis, characterized by iron accumulation, oxidative stress, lipid peroxidation, mitochondrial damage, an increased Bax/Bcl-2 ratio, Caspase-3 activation, and PARP1 cleavage. These changes significantly suppressed ccRCC cell proliferation, migration, and invasion. Integrated RNA sequencing and RIP sequencing analyses, together with molecular validation, identified Caveolin-1 (CAV1) as a downstream target of YTHDF1. Rescue experiments showed that CAV1 overexpression effectively reversed the ferroptotic and apoptotic phenotypes, as well as the impaired malignant behaviors, induced by YTHDF1 knockdown. In vivo, YTHDF1 depletion markedly inhibited xenograft tumor growth, whereas restoration of CAV1 reversed this tumor-suppressive effect and attenuated the associated ferroptosis- and apoptosis-related changes.Conclusions\n\nThis study identifies the YTHDF1/CAV1 signaling axis as a critical regulator that concurrently suppresses ferroptosis and apoptosis in ccRCC, highlighting it as a promising therapeutic target to inhibit ccRCC progression.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.",
    "Department of Urology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.",
    "Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, China.",
    "Department of Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China.",
    "Department of Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China. zxyyguda@163.com.",
    "Department of Urology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, China. renshancheng@gmail.com.",
    "Department of Urology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China. renshancheng@gmail.com.",
    "Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China. 122526195@qq.com.",
    "Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China. kangweiting@sdfmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yulin Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Songbo Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinpeng Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Shouwei Zhu"
    },
    {
      "affs": [
        3
      ],
      "name": "Huanmin Lou"
    },
    {
      "affs": [
        4
      ],
      "name": "Da Gu"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Shancheng Ren"
    },
    {
      "affs": [
        7
      ],
      "name": "Zilian Cui"
    },
    {
      "affs": [
        8
      ],
      "name": "Weiting Kang",
      "orcid": "0000-0002-5190-5817"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/frmvt5js1vw0b.bib",
  "cited_by": 0,
  "doi": "10.1186/s13062-026-00939-5",
  "fulltext_url": "https://europepmc.org/articles/PMC13753123",
  "id": "frmvt5js1vw0b",
  "issns": [
    "1745-6150"
  ],
  "landing_url": "https://europepmc.org/article/MED/43010063",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7202356123",
  "pdf_url": "https://europepmc.org/articles/PMC13753123?pdf=render",
  "pmcid": "PMC13753123",
  "pmid": "43010063",
  "published": "2026-08-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/frmvt5js1vw0b.ris",
  "sources": [
    {
      "first_seen": "2026-11-12T15:22:43Z",
      "native_id": "MED:43010063",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/43010063"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Ferroptosis and cancer prognosis",
      "subfield": "oncology"
    }
  ],
  "title": "The YTHDF1/CAV1 axis regulates clear cell renal cell carcinoma progression through ferroptosis and apoptosis.",
  "title_text": "The YTHDF1/CAV1 axis regulates clear cell renal cell carcinoma progression through ferroptosis and apoptosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T03:20:45Z",
  "url": "https://research.draconitic.com/paper/frmvt5js1vw0b",
  "venue": "Biology direct",
  "versions": []
}