c-MYC drives histone demethylase PHF8 during neuroendocrine differentiation and in castration-resistant prostate cancer

被引:45
|
作者
Maina, Peterson Kariuki [1 ]
Shao, Peng [1 ]
Liu, Qi [1 ]
Fazli, Ladan [2 ]
Tyler, Scott [1 ]
Nasir, Moman [3 ]
Dong, Xuesen [2 ]
Qi, Hank Heng [1 ]
机构
[1] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52246 USA
[2] Univ British Columbia, Dept Urol Sci, Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
[3] Univ Iowa, Coll Liberal Arts & Sci, Dept Hlth & Human Physiol, Iowa City, IA 52242 USA
关键词
prostate cancer; NED; CRPC; PHF8; c-MYC; ANDROGEN-RECEPTOR; GENE-EXPRESSION; CLIP-SEQ; INTERLEUKIN-6; TRANSCRIPTION; ACTIVATION; GROWTH; CELLS; IDENTIFICATION; REPRESSION;
D O I
10.18632/oncotarget.12310
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetic factors play critical roles in prostate cancer (PCa) development. However, how they contribute to neuroendocrine differentiation (NED) and castration-resistant PCa (CRPC) is not fully understood. Using bioinformatics and biochemical approaches to analyze cell-based models of NED and CRPC, we found a cluster of epigenetic factors whose expression is downregulated during NED and upregulated in CRPC (i.e. follow a Down-Up pattern). Two histone demethylases within this cluster, PHF8 and KDM3A, are post-transcriptionally regulated by c-MYC through miR-22, which targets both PHF8 and KDM3A. We also found that the c-MYC/miR22/PHF8 axis is downstream of androgen receptor (AR) signaling in CRPC cells. The co-expression of PHF8 with AR in clinical CRPC samples, normal mouse prostate, and adenocarcinomas of the prostate during PCa progression in a transgenic (TRAMP) mouse model supports the connection between PHF8 and AR. Knockdown of PHF8 impedes cell cycle progression in CRPC cells and has more profound effects on their growth than on the parental LNCaP cell line. Furthermore, PHF8 knockdown sensitizes LNCaP-Abl cells to the AR antagonist enzalutamide. Our data reveal novel mechanisms that underlie the regulation of PHF8 and KDM3A during NED and in CRPC, and support the candidacy of PHF8 as a therapeutic target in CRPC.
引用
收藏
页码:75585 / 75602
页数:18
相关论文
共 50 条
  • [31] Systematic knockdown of epigenetic enzymes identifies a novel histone demethylase PHF8 overexpressed in prostate cancer with an impact on cell proliferation, migration and invasion
    Bjorkman, M.
    Ostling, P.
    Harma, V.
    Virtanen, J.
    Mpindi, J-P
    Rantala, J.
    Mirtti, T.
    Vesterinen, T.
    Lundin, M.
    Sankila, A.
    Rannikko, A.
    Kaivanto, E.
    Kohonen, P.
    Kallioniemi, O.
    Nees, M.
    ONCOGENE, 2012, 31 (29) : 3444 - 3456
  • [32] Histone demethylase LSD1 promotes castration-resistant prostate cancer by causing widespread gene expression derangements
    Li, Haiying
    Fan, Xiujie
    Fang, Xiuxiu
    Wang, Yunshan
    IUBMB LIFE, 2025, 77 (03)
  • [33] Therapeutic targeting of histone lysine demethylase KDM4B blocks the growth of castration-resistant prostate cancer
    Duan, Lingling
    Chen, Yu-An
    Liang, Yanping
    Chen, Zhenhua
    Lu, Jun
    Fang, Yong
    Cao, Jiazheng
    Lu, Jian
    Zhao, Hongwei
    Pong, Rey-Chen
    Hernandez, Elizabeth
    Kapur, Payal
    Tran, Tram Anh T.
    Smith, Tristan
    Martinez, Elisabeth D.
    Ahn, Jung-Mo
    Hsieh, Jer-Tsong
    Luo, Jun-hang
    Liu, Zhi-Ping
    BIOMEDICINE & PHARMACOTHERAPY, 2023, 158
  • [34] Transcription factor Olig2 is a major downstream effector of histone demethylase Phf8 during oligodendroglial development
    Kremp, Marco
    Aberle, Tim
    Sock, Elisabeth
    Bohl, Bettina
    Hillgaertner, Simone
    Winkler, Juergen
    Wegner, Michael
    GLIA, 2024, 72 (08) : 1435 - 1450
  • [35] TNIK drives castration-resistant prostate cancer via phosphorylating EGFR
    Guo, Jianing
    Liang, Jiaming
    Wang, Youzhi
    Guo, Tao
    Liao, Yihao
    Zhong, Boqiang
    Guo, Shuyue
    Cao, Qian
    Li, Junbo
    Flores-Morales, Amilcar
    Niu, Yuanjie
    Jiang, Ning
    ISCIENCE, 2024, 27 (01)
  • [36] Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer
    Dong, Baijun
    Fan, Liancheng
    Wang, Yanqing
    Chi, Chenfei
    Ma, Xiaowei
    Wang, Rui
    Cai, Wen
    Shao, Xiaoguang
    Pan, Jiahua
    Zhu, Yinjie
    Xun Shangguan
    Xin, Zhixiang
    Hu, Jianian
    Xie, Shaowei
    Kang, Xiaonan
    Zhou, Lixin
    Xue, Wei
    PROSTATE, 2017, 77 (13): : 1373 - 1380
  • [37] A microRNA-based classifier for identification of neuroendocrine differentiation in metastatic castration-resistant prostate cancer.
    Saini, Sharanjot
    Bhagirath, Divya
    Patel, Nikhil
    Sharma, Ashok
    Lee, Tae Jin
    JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (06)
  • [38] TIMP-1: A potential biomarker of neuroendocrine differentiation in metastatic castration-resistant prostate cancer (mCRPC)
    Gong, Yixuan
    Chippada-Venkata, Uma
    Dai, Xudong
    Galsky, Matthew D.
    Huang, Jiaoti
    CANCER RESEARCH, 2014, 74 (19)
  • [39] The histone demethylase JMJD1A is essential to prostate cancer cells through regulation of c-Myc expression
    Fan, Lingling
    Peng, Guihong
    Sahgal, Natasha
    Fazli, Ladan
    Gleave, Martin
    Zhang, Yuji
    Hussain, Arif
    Qi, Jianfei
    CANCER RESEARCH, 2015, 75
  • [40] miRNA alterations associated with transition of advanced castration-resistant prostate cancer to neuroendocrine prostate cancer
    Bhagirath, Divya
    Yang, Thao
    Tabatabai, Laura
    Majid, Shahana
    Dahiya, Rajvir
    Tanaka, Yuichiro
    Saini, Sharanjot
    CANCER RESEARCH, 2019, 79 (13)