PBRM1 suppresses bladder cancer by cyclin B1 induced cell cycle arrest.
PBRM1 suppresses bladder cancer by cyclin B1 induced cell cycle arrest.
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PBRM1 通过细胞周期蛋白 B1 诱导的细胞周期阻滞抑制膀胱癌
DOI：
10.18632/oncotarget.3879
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发表时间：
2015-06-30
期刊：
影响因子：
--
通讯作者：
Huang J
中科院分区：
文献类型：
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作者：
Huang L;Peng Y;Zhong G;Xie W;Dong W;Wang B;Chen X;Gu P;He W;Wu S;Lin T;Huang J
越来越多的证据表明PBRM 1的失调有助于肿瘤发生。然而，关于PBRM 1在膀胱癌的发展或进展中的生物学功能知之甚少。在这项研究中，我们的目的是阐明PBRM 1在膀胱癌中的病理生理作用。我们评估了PBRM 1在64例膀胱癌组织样本和匹配的正常组织中的表达。我们在体外和体内研究了PBRM 1的生物学功能。分析PBRM 1的突变状态。评价PBRM 1对细胞周期的影响。采用qRT-PCR和Western blot检测PBRM 1对细胞周期蛋白表达的影响。我们的研究结果表明，PBRM 1的表达显着降低膀胱癌细胞和组织相比，他们的正常同行。PBRM 1的表达降低与肿瘤的晚期、低分化程度和较差的患者预后相关。进一步的功能分析表明PBRM 1抑制膀胱癌细胞的增殖、迁移、体外集落形成和体内致瘤性。遗传改变分析显示没有氨基酸序列改变突变。我们发现PBRM 1可以通过抑制cyclin B1来阻断G2/M转换。我们的数据表明PBRM 1通过抑制细胞周期蛋白B1的表达在膀胱癌中起肿瘤抑制剂的作用。
Growing evidence indicates that dys-regulation of PBRM1 contributes to tumorigenesis. However, little is known about the biological function of PBRM1 in the development or progression of bladder cancer. In this study, we aimed to elucidate the pathophysiological role of PBRM1 in bladder cancer. We assessed the expression of PBRM1 in 64 bladder cancer tissue samples with matching normal tissues. We explored the biological functions of PBRM1 both in vitro and in vivo. Mutational status of PBRM1 was analyzed. Effect of PBRM1 on cell cycle was evaluated. qRT-PCR and Western blot were carried out to evaluate the expression of cyclins affected by PBRM1. Our results showed that PBRM1 expression was significantly reduced in bladder cancer cells and tissues compared to their normal counterparts. The reduced expression of PBRM1 was associated with advanced tumor stage, low differentiation grade and worse patient outcome. Further functional analysis demonstrated that PBRM1 suppressed bladder cancer cell proliferation, migration, colony formation in vitro and tumorigenicity in vivo. Genetic alteration analysis showed no amino-acid sequence altering mutations. We found that PBRM1 could block the G2/M transition by repressing cyclin B1. Our data indicated that PBRM1 functions as a tumor suppressor in bladder cancer by repressing cyclin B1 expression.