Research Papers:

TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFβR2/p-Smad3 signals

Xiaofu Qiu _, Jin Zhu, Yin Sun, Kun Fan, Dong-Rong Yang, Gonghui Li, Guosheng Yang and Chawnshang Chang

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Oncotarget. 2015; 6:15397-15409. https://doi.org/10.18632/oncotarget.3778

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Xiaofu Qiu1,2,*, Jin Zhu3,*, Yin Sun2, Kun Fan1,2, Dong-Rong Yang3, Gonghui Li4, Guosheng Yang1,2, Chawnshang Chang2,5

1Department of Urology, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, China

2George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA

3Department of Urology, the Second Affiliated Hospital of Soochow University, Suzhou, China

4Chawnshang Chang Liver Cancer Center, Department of Urology, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China

5Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Guosheng Yang, e-mail: [email protected]

Chawnshang Chang, e-mail: [email protected]

Keywords: TR4, prostate cancer, metastasis, miR-373-3p

Received: January 07, 2015     Accepted: April 14, 2015     Published: April 27, 2015


Testicular nuclear receptor 4 (TR4), a member of the nuclear receptor superfamily, may play important roles to modulate the metabolic diseases and prostate tumorigenesis. Here we found TR4 could increase prostate cancer (PCa) cell invasion. Mechanism dissection revealed that TR4 might increase PCa cell invasion via decreasing the miR-373-3p expression that resulted in the activation of the TGFβR2/p-Smad3 signals. The in vivo mouse model using orthotopically xenografted CWR22Rv1 cell line transfected with luciferase-reporter confirmed in vitro cell line studies showing TR4 increased PCa metastasis via decreasing the miR-373-3p expression. Together, these data suggest that TR4 may increase PCa metastasis via a newly identified signal and targeting these TR4/miR-473-3p/TGFβR2/p-Smad3 signals using TR4 antagonist or TR4-siRNA or miR-373-3p may allow us to develop a new potential therapeutic approach to better suppress PCa metastasis.

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