Department of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China.
Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China.
Clin Transl Oncol. 2020 May;22(5):772-781. doi: 10.1007/s12094-019-02190-z. Epub 2019 Jul 31.
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.
鸡卵清蛋白上游启动子转录因子 II（COUP-TFII）可能是肾细胞癌（RCC）中的致癌基因。然而，COUP-TFII 表达与 RCC 患者生存之间的直接关联尚未在 RCC 患者中进行研究，COUP-TFII 在 RCC 中的分子致癌作用仍不清楚。
通过 RT-qPCR 测定了 283 例 RCC 患者肿瘤中的 COUP-TFII mRNA 表达水平。根据 ROC 分析生成的截断值，将另外 266 例患者分为低表达组和高表达组。在体外通过敲低实验测试 COUP-TFII 在 RCC 细胞中的功能。
本研究表明，COUP-TFII 的 mRNA 表达水平在肿瘤中明显高于相邻非癌组织，COUP-TFII 的过表达与患者生存不良密切相关。进一步证实，COUP-TFII 的敲低抑制了 RCC 细胞的增殖，并在体外诱导了细胞凋亡和细胞周期停滞。这也导致了线粒体介导的凋亡途径的激活，通过上皮-间充质转化损害了 RCC 细胞的迁移和侵袭能力，并抑制了体内肿瘤的生长。此外，研究表明 COUP-TFII 诱导的细胞迁移和侵袭至少部分是由整合素亚基β1 介导的。
总之，本研究表明 COUP-TFII 是 RCC 中的致癌基因，是治疗该疾病的潜在治疗靶点。
