title: EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells.
abstract: 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.
authors: Shandong University School of Life Sciences, Room 103, South Building, 27 Shanda South Road, Jinan, 250100 China.
authors: Jing
authors: J
authors: Cui
authors: The Second Hospital, Shandong University, Jinan, China.
authors: Wendong
authors: W
authors: Sun
authors: The Second Hospital, Shandong University, Jinan, China.
authors: Xuexi
authors: X
authors: Hao
authors: Shandong University School of Life Sciences, Room 103, South Building, 27 Shanda South Road, Jinan, 250100 China.
authors: Minli
authors: M
authors: Wei
authors: Shandong University School of Life Sciences, Room 103, South Building, 27 Shanda South Road, Jinan, 250100 China.
authors: Xiaonan
authors: X
authors: Su
authors: Shandong University School of Life Sciences, Room 103, South Building, 27 Shanda South Road, Jinan, 250100 China.
authors: Yajing
authors: Y
authors: Zhang
authors: Shandong University School of Life Sciences, Room 103, South Building, 27 Shanda South Road, Jinan, 250100 China.
authors: Ling
authors: L
authors: Su
authors: Shandong University School of Life Sciences, Room 103, South Building, 27 Shanda South Road, Jinan, 250100 China.
authors: Xiangguo
authors: X
authors: Liu
keywords: Apoptosis; BIX-01294; DDIT3; EHMT2; ER stress; MCL1; PMAIP1; USP9X