Oncotarget

Research Papers:

Androgen receptor regulates SRC expression through microRNA-203

Man Kit Siu, Wei-Yu Chen, Hong-Yuan Tsai, Hsiu-Lien Yeh, Juan Juan Yin, Shih-Yang Liu and Yen-Nien Liu _

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Oncotarget. 2016; 7:25726-25741. https://doi.org/10.18632/oncotarget.8366

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Abstract

Man Kit Siu1,2,3,*, Wei-Yu Chen4,5,*, Hong-Yuan Tsai2, Hsiu-Lien Yeh6, Juan Juan Yin7, Shih-Yang Liu8, Yen-Nien Liu1,2

1Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan

2Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

3Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

4Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

5Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

6Institute of Information System and Applications, National Tsing Hua University, Hsinchu, Taiwan

7Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

8Department of Andrology, Pingtan Hospital of Traditional Chinese Medicine, Fujian, China

*These authors have contributed equally to this work

Correspondence to:

Yen-Nien Liu, e-mail: [email protected]

Keywords: androgen receptor (AR), microRNA (miR)-203, prostate cancer (PCa), SRC

Received: December 03, 2015     Accepted: March 07, 2016     Published: March 25, 2016

ABSTRACT

The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures. Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3′ UTR of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens. We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203.


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