UCHL1 Is a Putative Tumor Suppressor in Ovarian Cancer Cells and Contributes to Cisplatin Resistance.
UCHL1 Is a Putative Tumor Suppressor in Ovarian Cancer Cells and Contributes to Cisplatin Resistance.
复制标题
DOI：
10.7150/jca.6641
复制
发表时间：
2013
影响因子：
3.9
通讯作者：
Lin B
中科院分区：
文献类型：
--
作者：
Jin C;Yu W;Lou X;Zhou F;Han X;Zhao N;Lin B
泛素羧基末端水解酶1（UCHL 1）催化羧基末端泛素酯和酰胺的水解。据报道，它在癌症中是癌基因或肿瘤抑制基因。然而，UCHL 1在卵巢癌中的作用仍不清楚。因此，我们进行了一项分析，以了解UCHL 1在卵巢癌中的作用。首先，我们检测了7种卵巢癌细胞系UCHL 1启动子甲基化状态。其中4例UCHL 1基因沉默的患者出现了严重的启动子甲基化，而另外3例UCHL 1基因高表达的患者出现了轻微的启动子甲基化。然后，我们降低了UCHL 1在卵巢癌细胞系A2780和IGROV 1中的表达，发现抑制UCHL 1通过增加细胞周期S期的细胞来促进细胞增殖。UCHL 1的敲低也减少了细胞凋亡，并有助于顺铂耐药。此外，UCHL 1在几种卵巢癌细胞系中的表达水平与其顺铂耐药水平呈负相关。微阵列数据显示，UCHL 1相关基因在细胞凋亡和细胞死亡基因本体论（GO）术语中富集。UCHL 1基因敲除后，凋亡相关基因BCL 2、BCL 11 A、AEN和XIAP表达增加。UCHL 1基因敲除细胞中Bcl-2和pAKT表达上调，Bax表达下调，而p53和AKT 1表达无明显变化，为通过UCHL 1介导的途径克服卵巢癌顺铂耐药提供了新的有前景的策略。
Ubiquitin carboxyl terminal hydrolase 1 (UCHL1) catalyzes the hydrolysis of COOH-terminal ubiquityl esters and amides. It has been reported as either an oncogene or a tumor suppressor in cancers. However, UCHL1's role in ovarian cancer is still unclear. Therefore, we conducted an analysis to understand the role of UCHL1 in ovarian cancer. Firstly, we detected UCHL1 promoter methylation status in 7 ovarian cancer cell lines. 4 of them with UCHL1 silencing showed heavy promoter methylation while the other 3 with relative high UCHL1 expression showed little promoter methylation. Then we reduced UCHL1 expression in ovarian cancer cell line A2780 and IGROV1 and found that inhibition of UCHL1 promoted cell proliferation by increasing cells in S phases of cell cycle. Knockdown of UCHL1 also reduced cell apoptosis and contributed to cisplatin resistance. Furthermore, the expression level of UCHL1 in several ovarian cancer cell lines correlated negatively with their cisplatin resistance levels. Microarray data revealed that UCHL1 related genes are enriched in apoptosis and cell death gene ontology (GO) terms. Several apoptosis related genes were increased after UCHL1 knockdown, including apoptosis regulator BCL2, BCL11A, AEN and XIAP. Furthermore, we identified up-regulation of Bcl-2 and pAKT as well as down-regulation of Bax in UCHL1 knockdown cells, while no significant alteration of p53 and AKT1 was found. This study provides a new and promising strategy to overcome cisplatin resistance in ovarian cancer via UCHL1 mediated pathways.
登录
查看更多内容
影响因子：
11.4
作者：
通讯作者：
--
DOI：
10.1016/j.ejogrb.2009.06.011
发表时间：
2009-10-01
影响因子：
2.6
作者：
Ma, Jia-jia;Chen, Bi-liang;Xin, Xiao-yan
通讯作者：
Xin, Xiao-yan
影响因子：
6.4
作者：
Okochi-Takada, Eriko;Nakazawa, Kazuyuki;Ushijima, Toshikazu
通讯作者：
Ushijima, Toshikazu
影响因子：
4.7
作者：
PETRU, E;SEVIN, BU;AVERETTE, HE
通讯作者：
AVERETTE, HE
影响因子：
3.7
作者：
Bonazzi VF;Nancarrow DJ;Stark MS;Moser RJ;Boyle GM;Aoude LG;Schmidt C;Hayward NK
通讯作者：
Hayward NK