Oncotarget

Research Papers:

FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription

Youhong Liu, Yijun Liu, Bowen Yuan, Linglong Yin, Yuchong Peng, Xiaohui Yu, Weibing Zhou, Zhicheng Gong, Jianye Liu, Leye He and Xiong Li _

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Oncotarget. 2017; 8:17027-17037. https://doi.org/10.18632/oncotarget.15224

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Abstract

Youhong Liu1,2,*, Yijun Liu1,2,*, Bowen Yuan1,2, Linglong Yin1,2, Yuchong Peng1,2, Xiaohui Yu1,2, Weibing Zhou3, Zhicheng Gong4, Jianye Liu5,6, Leye He5,6, Xiong Li1,2,6

1Center for Molecular Medicine, Xiangya Hospital, Central South University, China

2Hunan Key Laboratory of Molecular Radiation Oncology, Xiangya Hospital, Central South University, China

3Department of Oncology, Xiangya Hospital, Central South University, China

4Department of Pharmacy, Xiangya Hospital, Central South University, China

5Department of Urology, The Third Xiangya Hospital, Central South University, China

6Research Institute of Prostate Diseases, Central South University, China

*These authors equally contributed to this paper

Correspondence to:

Xiong Li, email: lixiongxiangya@csu.edu.cn

Keywords: PSA, FOXM1, gene transcription, androgen receptor, prostate cancer

Received: November 11, 2016     Accepted: January 09, 2017     Published: February 09, 2017

ABSTRACT

Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.


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