Oncotarget

Research Papers:

A dual yet opposite growth-regulating function of miR-204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrine-like prostate cancer cells

Miao Ding, Biaoyang Lin, Tao Li, Yuanyuan Liu, Yuhua Li, Xiaoyu Zhou, Maohua Miao, Jinfa Gu, Hongjie Pan, Fen Yang, Tianqi Li, Xin Yuan Liu and Runsheng Li _

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Oncotarget. 2015; 6:7686-7700. https://doi.org/10.18632/oncotarget.3480

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Abstract

Miao Ding1,2,3, Biaoyang Lin4,5, Tao Li6, Yuanyuan Liu2,3, Yuhua Li2,3, Xiaoyu Zhou2,3, Maohua Miao2,3, Jinfa Gu1, Hongjie Pan2,3, Fen Yang2,3, Tianqi Li2,3, Xin Yuan Liu1 and Runsheng Li2,3,6,7

1 State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China

2 WHO Collaborating Center for Research in Human Reproduction, Shanghai, China

3 Key Laboratory of Contraceptive Drugs and Devices of NPFPC, Shanghai Institute of Planned Parenthood Research, Shanghai, China

4 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

5 Department of Urology, University of Washington, Seattle, WA, USA

6 Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China

7 The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

8 Institute of Reproduction and Development, Fudan University, Shanghai, China

Correspondence to:

Runsheng Li, email:

Xin Yuan Liu, email:

Keywords: miR-204, XRN1, Prostate cancer

Received: December 07, 2014 Accepted: February 03, 2015 Published: March 08, 2015

Abstract

Androgen deprivation therapy in prostate cancer (PCa) causes neuroendocrine differentiation (NED) of prostatic adenocarcinomas (PAC) cells, leading to recurrence of PCa. Androgen-responsive genes involved in PCa progression including NED remain largely unknown. Here we demonstrated the importance of androgen receptor (AR)-microRNA-204 (miR-204)-XRN1 axis in PCa cell lines and the rat ventral prostate. Androgens downregulate miR-204, resulting in induction of XRN1 (5’-3’ exoribonuclease 1), which we identified as a miR-204 target. miR-204 acts as a tumor suppressor in two PAC cell lines (LNCaP and 22Rv1) and as an oncomiR in two neuroendocrine-like prostate cancer (NEPC) cell lines (PC-3 and CL1). Importantly, overexpression of miR-204 and knockdown of XRN1 inhibited AR expression in PCa cells. Repression of miR-34a, a known AR-targeting miRNA, contributes AR expression by XRN1. Thus we revealed the AR-miR-204-XRN1-miR-34a positive feedback loop and a dual function of miR-204/XRN1 axis in prostate cancer.


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