{
  "abstract": "Background: Advanced clear cell renal cell carcinoma (ccRCC) has a poor prognosis and frequent targeted therapy resistance, which urgently requires novel prognostic biomarkers and therapeutic targets. This study aimed to screen hub genes from our previously constructed ccRCC prognostic gene signature and clarify the oncogenic function and molecular mechanism of CXCL9 in ccRCC progression. Methods: Bioinformatic PPI network analysis was performed to screen candidate hub genes; qRT-PCR and IHC verified CXCL9 expression in clinical tissues and cell lines. Lentiviral shRNA was used to stably knock down CXCL9, followed by cell proliferation, apoptosis, migration, invasion and tube formation assays. Rescue experiments, transcriptomic and metabolomic sequencing, as well as subcutaneous xenograft mouse models were applied to validate molecular mechanisms and in vivo tumor phenotypes. TCGA-KIRC dataset was analyzed to evaluate correlations between CXCL9 expression, clinical parameters, sunitinib sensitivity and overall survival. Results: CXCL9 was determined as a hub gene and substantially upregulated in ccRCC. High CXCL9 expression correlated with distant metastasis, advanced pathological stage, shorter overall survival, and improved sunitinib sensitivity. CXCL9 knockdown suppressed ccRCC malignant phenotypes and angiogenesis, while inducing cell apoptosis. Mechanistically, CXCL9 bound CXCR3 to activate JAK-STAT3, EMT, and inflammatory pathways, which was further validated by multi-omics and rescue assays. In vivo assays further confirmed that CXCL9 silencing markedly restrained xenograft tumor growth. Conclusions: The CXCL9/CXCR3/JAK-STAT3 cascade serves as a core driver of ccRCC progression. CXCL9 can act as a novel prognostic biomarker and promising therapeutic target for ccRCC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, China–Japan Union Hospital of Jilin University, No. 126, Xiantai Road, Changchun, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shi Zong"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaichen Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yonggang Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fbajpccqk14ak.bib",
  "cited_by": 0,
  "doi": "10.32604/or.2026.084842",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732337/",
  "id": "fbajpccqk14ak",
  "issns": [
    "0965-0407",
    "1555-3906"
  ],
  "landing_url": "https://doi.org/10.32604/or.2026.084842",
  "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",
      "2730|Renal cell carcinoma treatment"
    ]
  ],
  "openalex": "W7221621532",
  "pdf_url": null,
  "pmcid": "PMC13732337",
  "pmid": "42985440",
  "published": "2026-10-28",
  "publisher": "Tech Science Press",
  "ris": "https://research.draconitic.com/paper/fbajpccqk14ak.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:20Z",
      "native_id": "PMC13732337",
      "source": "pmc",
      "url": "https://doi.org/10.32604/or.2026.084842"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Renal cell carcinoma treatment",
      "subfield": "oncology"
    }
  ],
  "title": "CXCL9 Knockdown Inhibits Tumor Progression and Angiogenesis in Clear Cell Renal Cell Carcinoma via JAK-STAT3 Signaling Pathway",
  "title_text": "CXCL9 Knockdown Inhibits Tumor Progression and Angiogenesis in Clear Cell Renal Cell Carcinoma via JAK-STAT3 Signaling Pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:20Z",
  "url": "https://research.draconitic.com/paper/fbajpccqk14ak",
  "venue": "Oncology Research",
  "versions": []
}