EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells

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• 作者：Jing Cui (1)
  Wendong Sun (2)
  Xuexi Hao (2)
  Minli Wei (1)
  Xiaonan Su (1)
  Yajing Zhang (1)
  Ling Su (1)
  Xiangguo Liu (1)
  
  1. Shandong University School of Life Sciences ; Room 103 ; South Building ; 27 Shanda South Road ; Jinan ; 250100 ; China
  2. The Second Hospital ; Shandong University ; Jinan ; China
  
• 关键词：Apoptosis ; PMAIP1 ; MCL1 ; USP9X ; DDIT3 ; ER stress ; EHMT2 ; BIX ; 01294
• 刊名：Cancer Cell International
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：1,405 KB
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• 刊物主题：Cancer Research; Cell Biology;
• 出版者：BioMed Central
• ISSN：1475-2867

文摘

BIX-01294, an euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor, has been reported to induce apoptosis in human neuroblastoma cells and inhibit the proliferation of bladder cancer cells. However, the definite mechanism of the apoptosis mediated by BIX-01294 in bladder cancer cells remains unclear. In the present study, we found that BIX-01294 induced caspase-dependent apoptosis in human bladder cancer cells. Moreover, our data show BIX-01294 stimulates endoplasmic reticulum stress (ER stress) and up-regulated expression of PMAIP1 through DDIT3 up-regulation. Furthermore, down-regulation of the deubiquitinase USP9X by BIX-01294 results in downstream reduction of MCL1 expression, leading to apoptosis eventually. Thus, our findings demonstrate PMAIP1-USP9X-MCL1 axis may contribute to BIX-01294-induced apoptosis in human bladder cancer cells.