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However, their specific role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, the microplastics in ccRCC tissues and normal adjacent tissues (NAT) are detected utilizing Py\u2010GC\/MS, LDIR, and SEM. Tumor functional assays are conducted to assess the effects of PS\u2010MPs on ccRCC cellular behaviors. Transcriptomic alterations induced by PS\u2010MPs are characterized via RNA\u2010sequencing (RNA\u2010seq) analysis. Key signaling pathways are investigated through immunoblotting, immunocytochemistry, and ELISA. PDO and CDX models are employed to evaluate the effects of PS\u2010MPs on ccRCC progression and intervention strategies. The results demonstrate that PS\u2010MPs are markedly abundant in ccRCC tissues compared to NAT. Cytoplasmic accumulation of PS\u2010MPs promotes malignant phenotypes in ccRCC cells. RNA\u2010seq analysis demonstrates significant enrichment of oncogenic pathways following PS\u2010MPs exposure. Mechanistic validation confirms PS\u2010MPs exposure activates the NF\u2010\u03baB and TGF\u2010\u03b2 pathways in ccRCC. In preclinical models, PS\u2010MPs accelerate ccRCC growth, which is attenuated by treatment with the pathway inhibitors. In conclusion, this study provides the first comprehensive evidence that PS\u2010MPs exacerbate ccRCC progression through activating the NF\u2010\u03baB and TGF\u2010\u03b2 pathways. These\u00a0findings establish PS\u2010MPs as an environmental risk factor for ccRCC and identify potential therapeutic targets to counteract PS\u2010MPs\u2010mediated oncogenic effects.<\/jats:p>","DOI":"10.1002\/advs.202518500","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T03:36:19Z","timestamp":1764300979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Polystyrene Microplastics Exposure Aggravates Clear Cell Renal Cell Carcinoma Progression via the NF\u2010\u03baB and TGF\u2010\u03b2 Signaling Pathways"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9070-443X","authenticated-orcid":false,"given":"Shiqi","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Shanghai Genitourinary Cancer Institute Fudan University 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