Oncotarget

Research Papers:

Rab27A overexpression promotes bladder cancer proliferation and chemoresistance through regulation of NF-κB signaling

Jia Liu, Xue Gong, Xingwang Zhu, Dongwei Xue, Yili Liu and Ping Wang _

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Oncotarget. 2017; 8:75272-75283. https://doi.org/10.18632/oncotarget.20775

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Abstract

Jia Liu1, Xue Gong1, Xingwang Zhu1, Dongwei Xue1, Yili Liu1 and Ping Wang1

1Department of Urology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China

Correspondence to:

Ping Wang, email: wangpingcmu@126.com

Keywords: Rab27A, bladder cancer, FAK, NF-κB

Received: May 16, 2017    Accepted: July 29, 2017    Published: September 08, 2017

ABSTRACT

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.


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