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Int J Biochem Cell Biol. 2016 Apr;73:30-40. doi: 10.1016/j.biocel.2016.01.018. Epub 2016 Jan 28.

A transcriptional target of androgen receptor, miR-421 regulates proliferation and metabolism of prostate cancer cells.

Author information

1
State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, China.
2
Center of Translational Medicine, Central Hospital of Zibo, Zibo, Shangdong Province, China.
3
Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
4
Center of Translational Medicine, Central Hospital of Zibo, Zibo, Shangdong Province, China. Electronic address: litaozhongguo@vip.163.com.
5
State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, China. Electronic address: yaoli@fudan.edu.cn.

Abstract

Prostate cancer is one of the most common malignancies, and microRNAs have been recognized to be involved in tumorigenesis of various kinds of cancer including prostate cancer (PCa). Androgen receptor (AR) plays a core role in prostate cancer progression and is responsible for regulation of numerous downstream targets including microRNAs. This study identified an AR-repressed microRNA, miR-421, in prostate cancer. Expression of miR-421 was significantly suppressed by androgen treatment, and correlated to AR expression in different prostate cancer cell lines. Furthermore, androgen-activated AR could directly bind to androgen responsive element (ARE) of miR-421, as predicted by bioinformatics resources and demonstrated by ChIP and luciferase reporter assays. In addition, over-expression of miR-421 markedly supressed cell viability, delayed cell cycle, reduced glycolysis and inhibited migration in prostate cancer cells. According to the result of miR-421 target genes searching, we focused on 4 genes NRAS, PRAME, CUL4B and PFKFB2 based on their involvement in cell proliferation, cell cycle progression and metabolism. The expression of these 4 downstream targets were significantly repressed by miR-421, and the binding sites were verified by luciferase assay. Additionally, we explored the expression of miR-421 and its target genes in human prostate cancer tissues, both in shared microarray data and in our own cohort. Significant differential expression and inverse correlation were found in PCa patients.

KEYWORDS:

Androgen receptor; Prostate cancer; miR-421

PMID:
26827675
DOI:
10.1016/j.biocel.2016.01.018
[Indexed for MEDLINE]

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