Orphan Nuclear Receptor COUP-TFII is an Oncogenic Gene in Renal Cell Carcinoma

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) may be an oncogenic gene in renal cell carcinoma (RCC). However, the direct association between COUP-TFII expression and patient survival has not been investigated in patients with RCC, and the molecular oncogenesis of COUP-TFII in RCC remains unclear. The mRNA expression levels of COUP-TFII in the tumors of 283 patients with RCC were determined by RT-qPCR. The remaining 266 patients were categorized into low- and high-expression groups according to the cut off value generated by receiver operating curve (ROC) analysis. The function of COUP-TFII in RCC cells was tested by knockdown experiments in vitro. In the present study, it was revealed that the mRNA expression levels of COUP-TFII were significantly higher in tumors compared with those in adjacent non-cancerous tissues, and that the overexpression of COUP-TFII was strongly associated with poor patient survival. It was further demonstrated that knockdown of COUP-TFII suppressed proliferation, and induced apoptosis and cell cycle arrest in RCC cells in vitro. This also resulted in the activation of the mitochondria-mediated apoptosis pathway, impaired migration and invasion of RCC cells through epithelial–mesenchymal transition in vitro, and suppressed tumor growth in vivo. In addition, it was revealed that the induction of cell migration and invasion by COUP-TFII was mediated, at least in part, by integrin subunit β1. In summary, the present study indicated that COUP-TFII is an oncogenic gene in RCC, and a potential therapeutic target for the treatment of the disease.