Oncotarget

Research Papers:

A dual yet opposite growthregulating function of miR204 and its target XRN1 in prostate adenocarcinoma cells and neuroendocrinelike prostate cancer cells

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

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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.