ZRANB1 Is an EZH2 Deubiquitinase and a Potential Therapeutic Target in Breast Cancer | Zendy

Peijing Zhang | Zendy; Zhenna Xiao | Zendy; Shouyu Wang | Zendy; Mutian Zhang | Zendy; Yongkun Wei | Zendy; Qinglei Hang | Zendy; Jongchan Kim | Zendy; Fan Yao | Zendy; Cristian RodriguezAguayo | Zendy; Baochau N. Ton | Zendy; Minjung Lee | Zendy; Yumeng Wang | Zendy; Zhicheng Zhou | Zendy; Liyong Zeng | Zendy; Xiaoyu Hu | Zendy; Sarah E. Lawhon | Zendy; Ashley N. Siverly | Zendy; Xiaohua Su | Zendy; Jia Li | Zendy; Xiaoping Xie | Zendy; Xuhong Cheng | Zendy; Liang-Chiu Liu | Zendy; Hui-Wen Chang | Zendy; ShuFen Chiang | Zendy; Gabriel López-Berestein | Zendy; Anil K. Sood | Zendy; Junjie Chen | Zendy; M. James You | Zendy; ShaoCong Sun | Zendy; Han Liang | Zendy; Yun Huang | Zendy; Xianbin Yang | Zendy; Deqiang Sun | Zendy; Yutong Sun | Zendy; MienChie Hung | Zendy; Li Ma | Zendy

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ZRANB1 Is an EZH2 Deubiquitinase and a Potential Therapeutic Target in Breast Cancer

Author(s) -

Peijing Zhang,

Zhenna Xiao,

Shouyu Wang,

Mutian Zhang,

Yongkun Wei,

Qinglei Hang,

Jongchan Kim,

Fan Yao,

Cristian RodriguezAguayo,

Baochau N. Ton,

Minjung Lee,

Yumeng Wang,

Zhicheng Zhou,

Liyong Zeng,

Xiaoyu Hu,

Sarah E. Lawhon,

Ashley N. Siverly,

Xiaohua Su,

Jia Li,

Xiaoping Xie,

Xuhong Cheng,

Liang-Chiu Liu,

Hui-Wen Chang,

ShuFen Chiang,

Gabriel López-Berestein,

Anil K. Sood,

Junjie Chen,

M. James You,

ShaoCong Sun,

Han Liang,

Yun Huang,

Xianbin Yang,

Deqiang Sun,

Yutong Sun,

MienChie Hung,

Li Ma

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.03.078

Subject(s) - ezh2 , cancer research , deubiquitinating enzyme , cancer , small interfering rna , breast cancer , biology , histone methyltransferase , gene knockdown , cancer cell , histone , rna , cell culture , ubiquitin , biochemistry , genetics , gene

Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC). Intriguingly, a small-molecule inhibitor of ZRANB1 destabilizes EZH2 and inhibits the viability of TNBC cells. In patients with breast cancer, ZRANB1 levels correlate with EZH2 levels and poor survival. These findings suggest the therapeutic potential for targeting the EZH2 deubiquitinase ZRANB1.

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