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LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

Author

Listed:
  • Jie Luo

    (University of Rochester)

  • Keliang Wang

    (University of Rochester
    The 4th Affiliated Hospital of Harbin Medical University)

  • Shuyuan Yeh

    (University of Rochester)

  • Yin Sun

    (University of Rochester)

  • Liang Liang

    (Shanxi Province People’s Hospital)

  • Yao Xiao

    (University of Rochester)

  • Wanhai Xu

    (The 4th Affiliated Hospital of Harbin Medical University)

  • Yuanjie Niu

    (Tianjin Medical University)

  • Liang Cheng

    (Indiana University)

  • Sankar N. Maity

    (The University of Texas MD Anderson Cancer Center)

  • Runze Jiang

    (Jiangmen Maternity and Child Health Care Hospital)

  • Chawnshang Chang

    (University of Rochester
    China Medical University and Hospital)

Abstract

While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients’ survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression.

Suggested Citation

  • Jie Luo & Keliang Wang & Shuyuan Yeh & Yin Sun & Liang Liang & Yao Xiao & Wanhai Xu & Yuanjie Niu & Liang Cheng & Sankar N. Maity & Runze Jiang & Chawnshang Chang, 2019. "LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09784-9
    DOI: 10.1038/s41467-019-09784-9
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    Cited by:

    1. Marco Bolis & Daniela Bossi & Arianna Vallerga & Valentina Ceserani & Manuela Cavalli & Daniela Impellizzieri & Laura Di Rito & Eugenio Zoni & Simone Mosole & Angela Rita Elia & Andrea Rinaldi & Ricar, 2021. "Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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