Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells

Ai-Yu Gong1, Alex N Eischeid1, Jing Xiao1, Jian Zhao12, Dongqing Chen1, Zhao-Yi Wang1, Charles YF Young3 and Xian-Ming Chen1*

Author Affiliations

1 Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, 68178, USA

2 Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Science, Sichuan University, Chengdu, 610064, China

3 Department of Urology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

For all author emails, please log on.

BMC Cancer 2012, 12:492  doi:10.1186/1471-2407-12-492

Published: 24 October 2012

Abstract

Background

Androgen receptor (AR) signalling is critical to the initiation and progression of prostate cancer (PCa). Transcriptional activity of AR involves chromatin recruitment of co-activators, including the p300/CBP-associated factor (PCAF). Distinct miRNA expression profiles have been identified in PCa cells during the development and progression of the disease. Whether miRNAs regulate PCAF expression in PCa cells to regulate AR transcriptional activity is still unclear.

Methods

Expression of PCAF was investigated in several PCa cell lines by qRT-PCR, Western blot, and immunocytochemistry. The effects of PCAF expression on AR-regulated transcriptional activity and cell growth in PCa cells were determined by chromatin immunoprecipitation, reporter gene construct analysis, and MTS assay. Targeting of PCAF by miR-17-5p was evaluated using the luciferase reporter assay.

Results

PCAF was upregulated in several PCa cell lines. Upregulation of PCAF promoted AR transcriptional activation and cell growth in cultured PCa cells. Expression of PCAF in PCa cells was associated with the downregulation of miR-17-5p. Targeting of the 3’-untranslated region of PCAF mRNA by miR-17-5p caused translational suppression and RNA degradation, and, consequently, modulation of AR transcriptional activity in PCa cells.

Conclusions

PCAF is upregulated in cultured PCa cells, and upregulation of PCAF is associated with the downregulation of miR-17-5p. Targeting of PCAF by miR-17-5p modulates AR transcriptional activity and cell growth in cultured PCa cells.