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Sci Rep. 2016 Sep 29;6:34529. doi: 10.1038/srep34529.

Regulation of PCGEM1 by p54/nrb in prostate cancer.

Author information

1
Department of Pharmacology and Toxicology, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
2
Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA.
3
Department of Biochemistry, Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
4
Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
5
System Biosciences, Mountain View, CA, USA.
6
Department of Pulmonary Medicine, Tongji Hospital, Tongji University, Shanghai, China.
7
Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
8
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.

Abstract

PCGEM1 is a long non-coding RNA (lncRNA) that is often upregulated in prostate cancer. However, little is known how PCGEM1 is regulated. In the present study, we show transcriptional regulation of PCGEM1 in response to androgen deprivation by p54/nrb. While ectopic expression of p54/nrb increases, suppression of p54/nrb by RNAi or knockout (KO) reduces PCGEM1. Moreover, rescue experiments indicate that re-expression of p54/nrb in KO cells restores the ability to induce PCGEM1, leading to upregulation of the androgen receptor splice variant AR3 which has been shown to play a role in castration resistance. Finally, 3,3'-Diindolylmethane (DIM), a known chemoprevention agent, is capable of suppressing PCGEM1 expression by preventing the interaction of p54/nrb with the PCGEM1 promoter. In particular, DIM reduces tumor growth by suppression of PCGEM1 and promoting apoptosis in the castrated xenograft mouse model. Together, these results demonstrate a novel mechanism of p54/nrb-mediated expression of PCGEM1 and AR3, contributing to castration resistance in prostate cancer.

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