BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1

Sen Zhu; Dongyu Zhao; Lin Yan; Weihua Jiang; Jung Sun Kim; Bingnan Gu; Qipeng Liu; Rui Wang; Bo Xia; Jonathan C. Zhao; Gang Song; Wenyi Mi; Rong Fu Wang; Xiaobing Shi; Hung Ming Lam; Xuesen Dong; Jindan Yu; Kaifu Chen; Qi Cao

doi:10.1038/s41467-018-02863-3

BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1

Sen Zhu, Dongyu Zhao, Lin Yan, Weihua Jiang, Jung Sun Kim, Bingnan Gu, Qipeng Liu, Rui Wang, Bo Xia, Jonathan C. Zhao, Gang Song, Wenyi Mi, Rong Fu Wang, Xiaobing Shi, Hung Ming Lam, Xuesen Dong, Jindan Yu, Kaifu Chen, Qi Cao

Epigenetics & Molecular Carcinogenesis

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression. BMI1 binds the androgen receptor (AR) and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment. These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.

Original language	English (US)
Article number	500
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-02863-3
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Zhu, S., Zhao, D., Yan, L., Jiang, W., Kim, J. S., Gu, B., Liu, Q., Wang, R., Xia, B., Zhao, J. C., Song, G., Mi, W., Wang, R. F., Shi, X., Lam, H. M., Dong, X., Yu, J., Chen, K., & Cao, Q. (2018). BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1. Nature communications, 9(1), Article 500. https://doi.org/10.1038/s41467-018-02863-3

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abstract = "BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression. BMI1 binds the androgen receptor (AR) and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment. These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.",

author = "Sen Zhu and Dongyu Zhao and Lin Yan and Weihua Jiang and Kim, {Jung Sun} and Bingnan Gu and Qipeng Liu and Rui Wang and Bo Xia and Zhao, {Jonathan C.} and Gang Song and Wenyi Mi and Wang, {Rong Fu} and Xiaobing Shi and Lam, {Hung Ming} and Xuesen Dong and Jindan Yu and Kaifu Chen and Qi Cao",

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AU - Gu, Bingnan

AU - Liu, Qipeng

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AU - Xia, Bo

AU - Zhao, Jonathan C.

AU - Song, Gang

AU - Mi, Wenyi

AU - Wang, Rong Fu

AU - Shi, Xiaobing

AU - Lam, Hung Ming

AU - Dong, Xuesen

AU - Yu, Jindan

AU - Chen, Kaifu

AU - Cao, Qi

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BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1

Abstract

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