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Background <p>Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, presenting significant challenges in diagnosis and treatment. Despite recent advancements in targeted therapies and immune checkpoint inhibitors, drug resistance remains a major obstacle in metastatic ccRCC. As a member of the AAA + ATPase superfamily, TRIP13 has been implicated in tumorigenesis across various cancers. however, its specific role and underlying mechanisms in ccRCC are not yet fully understood. This study aimed to explore the functional role and mechanisms of TRIP13 in ccRCC progression and its potential as a therapeutic target.</p> Methods <p>Bioinformatics analyses were conducted to assess the expression, prognostic significance, clinical relevance, and oncogenic role of TRIP13 in ccRCC patients. In vitro, cell viability, cycle progression, apoptosis, and migration/invasion were evaluated using CCK-8, colony formation, EdU, flow cytometry, wound healing, and transwell assays. In vivo tumorigenic potential was assessed through a nude mouse xenograft model. Protein expression and interactions were analyzed by western blotting, co-immunoprecipitation, and RT-qPCR.</p> Results <p>We demonstrated that TRIP13 was significantly upregulated in ccRCC tissues and correlates with poor prognosis, advanced tumor grade, and metastasis. Additionally, we uncovered an interdependent relationship between TRIP13 expression, immune cell infiltration, immune checkpoints, and drug resistance. Functional assays revealed that TRIP13 promotes ccRCC cell proliferation, migration, and invasion in vitro, as well as tumorigenesis in vivo. Mechanistically, TRIP13 activates the PI3K/AKT/mTOR pathway and enhances cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process by upregulating NUSAP1.</p> Conclusions <p>TRIP13 is upregulated in ccRCC and may serve as a novel prognostic biomarker for patient survival and treatment response. Additionally, TRIP13 enhances ccRCC cell proliferation, invasion, and EMT via the PI3K/AKT/mTOR pathway, while its expression is closely linked to immune cell infiltration and immune checkpoint regulation, offering new insights for immunotherapeutic approaches in ccRCC.</p>

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TRIP13-induced NUSAP1 upregulation promotes CcRCC progression through EMT and PI3K/AKT/mTOR pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月11日

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  • Xiaolong Chen,
  • Qing Wang,
  • Zhiqiang Zhu,
  • Zheng Peng,
  • Kunyuan Huang,
  • Guanyun Deng,
  • Kehua Jiang,
  • Kun Chen,
  • Fa Sun

摘要

Background

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, presenting significant challenges in diagnosis and treatment. Despite recent advancements in targeted therapies and immune checkpoint inhibitors, drug resistance remains a major obstacle in metastatic ccRCC. As a member of the AAA + ATPase superfamily, TRIP13 has been implicated in tumorigenesis across various cancers. however, its specific role and underlying mechanisms in ccRCC are not yet fully understood. This study aimed to explore the functional role and mechanisms of TRIP13 in ccRCC progression and its potential as a therapeutic target.

Methods

Bioinformatics analyses were conducted to assess the expression, prognostic significance, clinical relevance, and oncogenic role of TRIP13 in ccRCC patients. In vitro, cell viability, cycle progression, apoptosis, and migration/invasion were evaluated using CCK-8, colony formation, EdU, flow cytometry, wound healing, and transwell assays. In vivo tumorigenic potential was assessed through a nude mouse xenograft model. Protein expression and interactions were analyzed by western blotting, co-immunoprecipitation, and RT-qPCR.

Results

We demonstrated that TRIP13 was significantly upregulated in ccRCC tissues and correlates with poor prognosis, advanced tumor grade, and metastasis. Additionally, we uncovered an interdependent relationship between TRIP13 expression, immune cell infiltration, immune checkpoints, and drug resistance. Functional assays revealed that TRIP13 promotes ccRCC cell proliferation, migration, and invasion in vitro, as well as tumorigenesis in vivo. Mechanistically, TRIP13 activates the PI3K/AKT/mTOR pathway and enhances cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process by upregulating NUSAP1.

Conclusions

TRIP13 is upregulated in ccRCC and may serve as a novel prognostic biomarker for patient survival and treatment response. Additionally, TRIP13 enhances ccRCC cell proliferation, invasion, and EMT via the PI3K/AKT/mTOR pathway, while its expression is closely linked to immune cell infiltration and immune checkpoint regulation, offering new insights for immunotherapeutic approaches in ccRCC.