PSMD14 Drives Clear Cell Renal Cell Carcinoma Progression via JAK/STAT3 Signaling

• Wenying Zhang

  Department of Nephrology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China

• Hui Di

  Department of Nephrology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China

• Renpei Xia

  Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing 401147, China

• Jiali Yang

  Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing 401147, China

• Junfeng Zhang

  Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing 401147, China

• Jianyou Gu

  Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing 401147, China

Cancer hallmarks include senescence, uncontrolled proliferation, and metastasis. We focused on 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a gene identified from a cellular senescence-related gene signature. We focused on PSMD14, a senescence-associated gene overexpressed in various tumors, to understand its clinical and tumorigenic roles in ccRCC. Based on 279 cellular senescence-related genes collected from the CellAge database, we constructed a prognostic signature for ccRCC patients using TCGA and ArrayExpress datasets. PSMD14 was significantly overexpressed in ccRCC tissues, correlating with malignancy andzidentified as an independent prognostic factor. Single-cell analysis further suggested that PSMD14 expression was associated with malignant cellular phenotypes and activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Functional experiments showed PSMD14's role in enhancing ccRCC cell proliferation, migration, and invasion via this pathway. In vivo, PSMD14 knockdown significantly reduced tumor growth and JAK/STAT3 pathway activity. Our study positions PSMD14 as a key oncogenic factor in ccRCC, offering a potential therapeutic target.

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