Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells.
Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells.
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Pokemon 沉默通过 Fas 和线粒体介导的途径增强肝细胞癌细胞中的 Caspase 依赖性细胞凋亡
DOI：
10.1371/journal.pone.0068981
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ren JL
中科院分区：
文献类型：
--
作者：
Zhang YQ;Xiao CX;Lin BY;Shi Y;Liu YP;Liu JJ;Guleng B;Ren JL
Pokemon(POK红系髓系致癌因子)是最近发现的一种具有原癌活性的POK转录因子，其在肝细胞癌发生中的作用仅被少数研究所证实。我们先前的研究发现，Pokemon在肝细胞癌中过表达，并通过AKT和ERK依赖的方式促进肝癌细胞的增殖和迁移。在本研究中，我们使用TUNEL法和FACS分析证明奥沙利铂诱导的细胞凋亡在沉默的精灵宝可梦细胞中显著增加。Western blotts显示，Pokemon缺陷细胞中P53的表达和磷酸化显著增加，从而启动了线粒体和死亡受体介导的细胞凋亡途径。在线粒体介导的途径中，促凋亡的Bad、Bid、Bim和Puma家族成员以及AIF的表达增加，线粒体膜电位降低，导致细胞色素C从线粒体释放出来。此外，奥沙利铂处理精灵宝可梦沉默细胞时，Fas受体、FADD及其下游靶标caspase-10和caspase-8被激活，导致caspase-8活性片段p18和p10释放增加。与对照组相比，在HepG2 si-Pokemon细胞中，激活的caspase-8介导的caspase-9和caspase-3下游效应酶的切割和激活增加。因此，精灵宝可梦可能是肝癌细胞内源性和外源性凋亡途径之间串扰的重要中介。此外，我们的发现表明，精灵宝可梦可能是人类癌症治疗的一个有吸引力的治疗靶点基因。
The role of Pokemon (POK erythroid myeloid ontogenic actor), a recently identified POK transcription factor with proto-oncogenic activity, in hepatocellular carcinogenesis has only been assessed by a few studies. Our previous study revealed that Pokemon is overexpressed in hepatocellular carcinomas (HCC) and promotes HCC cell proliferation and migration via an AKT- and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS analysis to demonstrate that oxaliplatin induced apoptosis was significantly increased in cells with silenced Pokemon. Western blots showed that p53 expression and phosphorylation were significantly increased in Pokemon defective cells, thereby initiating the mitochondria-mediated and death receptor-mediated apoptotic pathways. In the mitochondria-mediated pathway, expression of pro-apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma) as well as AIF was increased and decreasing the mitochondrial membrane potential resulted in cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition, upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and their downstream targets caspase-10 and caspase-8 were activated, causing increased release of caspase-8 active fragments p18 and p10. Increased activated caspase-8-mediated cleavage and activation of downstream effector caspases such as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to control. Therefore, Pokemon might serve as an important mediator of crosstalk between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our findings suggest that Pokemon could be an attractive therapeutic target gene for human cancer therapy.
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影响因子：
3.8
作者：
Avery-Kiejda KA;Bowden NA;Croft AJ;Scurr LL;Kairupan CF;Ashton KA;Talseth-Palmer BA;Rizos H;Zhang XD;Scott RJ;Hersey P
通讯作者：
Hersey P
口袋妖怪的沉默通过抑制PI3K/AKT途径来减轻体外和体内肝细胞癌细胞的增殖。
影响因子：
3.7
作者：
Lin CC;Zhou JP;Liu YP;Liu JJ;Yang XN;Jazag A;Zhang ZP;Guleng B;Ren JL
通讯作者：
Ren JL
DOI：
10.1074/jbc.m310240200
发表时间：
2004-03-19
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Laudes M;Christodoulides C;Sewter C;Rochford JJ;Considine RV;Sethi JK;Vidal-Puig A;O'Rahilly S
通讯作者：
O'Rahilly S
影响因子：
8
作者：
Davies, JM;Hawe, N;Zelent, A
通讯作者：
Zelent, A
影响因子：
4.8
作者：
Lee, DK;Suh, D;Hur, MW
通讯作者：
Hur, MW