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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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Orphan nuclear receptor COUP-TFII is an oncogenic gene in renal cell carcinoma

X Fang1, C-X Liu1, X-R Zeng1

  • 1Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|August 2, 2019
PubMed
Abstract

Insights

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is overexpressed in renal cell carcinoma (RCC) and linked to poor survival. Targeting COUP-TFII may offer a new therapeutic strategy for RCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is implicated in renal cell carcinoma (RCC) pathogenesis.
  • The direct correlation between COUP-TFII expression and RCC patient survival, as well as its specific oncogenic mechanisms, remain largely unexplored.

Purpose of the Study:

  • To investigate the association between COUP-TFII expression levels and patient survival in RCC.
  • To elucidate the molecular mechanisms underlying COUP-TFII's role in RCC oncogenesis.

Main Methods:

  • Quantified COUP-TFII mRNA expression in 283 RCC tumors using RT-qPCR.
  • Categorized 266 patients into low- and high-expression groups based on ROC analysis.
  • Performed in vitro knockdown experiments to assess COUP-TFII function in RCC cells.

Main Results:

  • COUP-TFII mRNA levels were significantly elevated in RCC tumors compared to adjacent non-cancerous tissues.
  • High COUP-TFII expression strongly correlated with poorer patient survival.
  • Knockdown of COUP-TFII inhibited RCC cell proliferation, induced apoptosis and cell cycle arrest, activated mitochondria-mediated apoptosis, and reduced migration and invasion via epithelial-mesenchymal transition.
  • COUP-TFII promoted tumor growth in vivo and its pro-migratory/invasive effects were partly mediated by integrin subunit β1.

Conclusions:

  • COUP-TFII functions as an oncogenic gene in renal cell carcinoma.
  • COUP-TFII represents a promising therapeutic target for RCC treatment.
Keywords:
COUP-TFIIIntegrin subunit beta 1Renal cell carcinoma

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