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

Xiaolong Chen1,2, Qing Wang2, Zhiqiang Zhu3

  • 1Guizhou University Medical College, Guiyang, Guizhou, China.

Journal of Translational Medicine
|August 12, 2025
PubMed
Abstract

Insights

Thyroid hormone receptor interacting protein 13 (TRIP13) is upregulated in clear cell renal cell carcinoma (ccRCC) and promotes tumor progression. Targeting TRIP13 may offer new therapeutic strategies for ccRCC, potentially improving patient outcomes and overcoming drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer subtype, with drug resistance posing a significant challenge.
  • Thyroid hormone receptor interacting protein 13 (TRIP13), an AAA+ ATPase, is implicated in various cancers, but its role in ccRCC is unclear.

Purpose of the Study:

  • To investigate the functional role and underlying mechanisms of TRIP13 in ccRCC progression.
  • To evaluate TRIP13 as a potential therapeutic target for ccRCC.

Main Methods:

  • Bioinformatics analyses assessed TRIP13 expression, prognostic value, and clinical relevance in ccRCC.
  • In vitro assays (CCK-8, colony formation, EdU, flow cytometry, wound healing, transwell) evaluated cell viability, cycle, apoptosis, migration, and invasion.
  • In vivo studies used a nude mouse xenograft model; protein expression and interactions were analyzed via western blotting, co-immunoprecipitation, and RT-qPCR.

Main Results:

  • TRIP13 was significantly upregulated in ccRCC tissues, correlating with poor prognosis, advanced grade, and metastasis.
  • TRIP13 promotes ccRCC cell proliferation, migration, invasion, and tumorigenesis in vitro and in vivo.
  • TRIP13 activates the PI3K/AKT/mTOR pathway, enhancing proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) by upregulating NUSAP1.

Conclusions:

  • TRIP13 is a potential prognostic biomarker for ccRCC patient survival and treatment response.
  • TRIP13 enhances ccRCC progression and EMT via the PI3K/AKT/mTOR pathway.
  • TRIP13 expression links to immune cell infiltration and checkpoint regulation, suggesting potential for immunotherapeutic strategies.
Keywords:
Clear cell renal cell carcinomaEMTNUSAP1PI3K/AKT/mTORTRIP13

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