Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling.
Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling.
复制标题
DOI：
10.18632/oncotarget.20775
复制
发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Liu J;Gong X;Zhu X;Xue D;Liu Y;Wang P
Rab 27 A的过度表达已在人类癌症中发现。然而，Rab 27 A在膀胱癌组织和细胞系中的临床意义和生物学效应尚未研究。本文应用免疫组化方法检测了87例膀胱癌组织中Rab 27 A蛋白的表达。我们发现Rab 27 A在87例癌症病例中的39例（44.8%）中过表达。Rab 27与浸润深度之间存在显著相关性（p=0.0083）。我们在5637细胞系中敲低Rab 27 A，并将Rab 27 A质粒转染BIU-87细胞系。Rab 27 A缺失抑制细胞生长速率和侵袭，而其过表达诱导细胞生长和侵袭。Rab 27 A在体内也促进癌细胞生长。细胞活力和Annexin V/PI染色表明，Rab 27 A维持癌细胞存活，并降低顺铂处理时的凋亡率。JC-1染色显示Rab 27 A上调线粒体膜电位。Western blot结果显示Rab 27 A过表达可上调cyclin D1、cyclin E、p-IκB、p-p65、Bcl-2、cIAP 1、cIAP 2蛋白表达。NF-κB抑制剂BAY 11-7082可阻断Rab 27对顺铂耐药和Bcl-2蛋白表达的影响。综上所述，Rab 27 A过表达可能通过调节NF-κB信号通路促进膀胱癌的生长、侵袭和化疗耐药。
Overexpression of Rab27A has been found in human cancers. However, the clinical significance and biological effects of Rab27A in bladder cancer tissues and cell lines have not been investigated. Here, we checked Rab27A protein in 87 cases of bladder cancer using immunohistochemistry. We found that Rab27A was overexpressed in 39 of 87 (44.8%) cancer cases. Significant association was found between Rab27 and invading depth (p=0.0083). We knocked down Rab27A in 5637 cell line and transfected Rab27A plasmid in BIU-87 cell line. Rab27A depletion inhibited cell growth rate and invasion while its overexpression induced cell growth and invasion. Rab27A also promoted cancer cell growth in vivo. Cell viability and Annexin V/PI staining demonstrated that Rab27A maintained cancer cell survival and reduced apoptosis rate when treated with cisplatin. JC-1 staining showed that Rab27A upregulated mitochondrial membrane potential. Western blot demonstrated that Rab27A overexpression upregulated cyclin D1, cyclin E, p-IκB, p-p65, Bcl-2, cIAP1, cIAP2 protein expression. NF-κB inhibitor BAY 11-7082 abolished the effects of Rab27 on cisplatin resistance and Bcl-2 protein. In conclusion, the present study demonstrated that Rab27A overexpression facilitates bladder cancer growth, invasion and chemoresistance in bladder cancer, possibly through regulation of NF-κB signaling pathway.