Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells

COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. By using RT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP-TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1. This article is protected by copyright. All rights reserved.

International journal of cancer. 2016 May 19 [Epub ahead of print]

Jia Zheng, Weijun Qin, Dian Jiao, Jing Ren, Ming Wei, Shengjia Shi, Wenjin Xi, He Wang, An-Gang Yang, Yi Huan, Weihong Wen

Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038, Xi'an, China., Department of Urology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, China., Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038, Xi'an, China., Department of Radiology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, China., Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038, Xi'an, China., State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032, Xi'an, China., State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032, Xi'an, China., Department of Urology, Tangdu Hospital, Fourth Military Medical University, 710038, Xi'an, China., State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032, Xi'an, China., Department of Radiology, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, China., State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032, Xi'an, China.