期刊
ONCOTARGET
卷 6, 期 10, 页码 7686-7700出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3480
关键词
miR-204; XRN1; Prostate cancer
资金
- National Natural Science Foundation of China [81270760]
- National Basic Research Program of China [2014CB943104, 2010CB529901, 2011CB510100]
- Shanghai Municipal Committee of Science and Technology [09140903200]
- Natural Science Foundation of Shanghai [13ZR1446300, 14ZR1435400]
- Zhejiang Sci-Tech University [1204807-Y]
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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