Androgen receptor is negatively correlated with the methylation-mediated transcriptional repression of miR-375 in human prostate cancer cells

Chu,Mingliang; Chang,Yunli; Li,Ping; Guo,Yanjing; Zhang,Kaiqing; Gao,Weiqiang

doi:10.3892/or.2013.2810

Androgen receptor is negatively correlated with the methylation-mediated transcriptional repression of miR-375 in human prostate cancer cells

Authors:
- Mingliang Chu
- Yunli Chang
- Ping Li
- Yanjing Guo
- Kaiqing Zhang
- Weiqiang Gao
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Affiliations: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
Published online on: October 24, 2013 https://doi.org/10.3892/or.2013.2810
Pages: 34-40
Copyright: © Chu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Androgen receptor (AR) plays a critical role during the development and progression of prostate cancer in which microRNA miR-375 is overexpressed and correlated with tumor progression. Although DNA methylation is a key mechanism for the repression of gene expression, the relationship between AR and the expression or the hypermethylation of miR-375 is unknown. In this study, we found that AR-positive prostate cancer (PCa) cells showed high expression levels and hypomethylation of the miR-375. In contrast, AR-negative PCa cells displayed low levels and hypermethylation of the miR-375. Addition of 5-Aza-2'-deoxycytidine, a specific inhibitor of DNA methylation, into the culture medium reversed the low expression levels of miR-375 in the AR negative PCa cells. In addition, the total activity levels of DNA methyltransferases (DNMTs) were high in AR-negative PCa cells, in which hypermethylation of miR-375 promoter and low expression levels of miR-375 were observed. Taken together, these findings indicate that the negative correlation between AR and total DNMT activity is one of mechanisms to influence the methylation status of miR-375 promoter, which in turn regulates the expression of miR-375.

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