Oncotarget

Research Papers:

Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

Yuan Chen, Yin Sun, Qun Rao, Hua Xu, Lei Li and Chawnshang Chang _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:31203-31215. https://doi.org/10.18632/oncotarget.4522

Metrics: PDF 1191 views  |   HTML 1280 views  |   ?  


Abstract

Yuan Chen1,3, Yin Sun3, Qun Rao2,3, Hua Xu3, Lei Li3 and Chawnshang Chang3,4

1 Sex Hormone Research Center, Department of Urology, Tongji Medical College/Hospital, Huazhong University of Science and Technology, Wuhan, China

2 Department of Gynaecology and Obstetrics, Tongji Medical College/Hospital, Huazhong University of Science and Technology, Wuhan, China

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

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

Correspondence to:

Chawnshang Chang, email:

Hua Xu, email:

Keywords: renal cell carcinoma, androgen receptor, microRNA-145, HIF2α

Received: December 30, 2014 Accepted: April 23, 2015 Published: August 18, 2015

Abstract

Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53’s ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 4522