URGCP/URG4 promotes apoptotic resistance in bladder cancer cells by activating NF-κB signaling
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Minglong Wu1,*, Junxing Chen3,*, Yuxi Wang2, Jinqian Hu2, Chang Liu2, Chunxiang Feng2, Xiaoyong Zeng2
1Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
3Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
*These authors have contributed equally to this work
Xiaoyong Zeng, e-mail: firstname.lastname@example.org
Keywords: bladder cancer, URGCP/URG4, apoptosis, NF-κB
Received: February 27, 2015 Accepted: August 20, 2015 Published: September 02, 2015
Cisplatin is a well-known chemotherapeutic agent, it could cause DNA damage and induce apoptotic cell death, but the cisplatin resistance also appears, it's important to reveal the mechanisms of cisplatin resistance . URGCP/URG4 is overexpressed in various tumors and plays critical role during tumor development. We found URGCP/URG4 was upregulated in bladder cancer cells and tissues, URGCP/URG4 overexpression increased the resistance to cisplatin-induced apoptosis in bladder cancer, and promoted anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and downregulated Caspase-3 expression, Knockdown of URGCP/URG4 decreased the resistance to cisplatin-induced apoptosis, and inhibited anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and upregulated Caspase-3 expression. Mechanism analysis found URGCP/URG4 activated NF-κB pathway which is a well-known anti-apoptotic pathway and promoted the expression of NF-κB targeted genes. So we speculated URGCP/URG4 regulates cisplatin-induced apoptosis by activating NF-κB pathway. We also analyzed the correlation between URGCP/URG4 expression and clinical clinicopathologic, and found its expression was positively correlated with bladder cancer progression, it can serve as a valuable prognostic factor. In summary, URGCP/URG4 promotes the resistance to cisplatin-induced apoptosis by activating NF-κB pathway, and is an unfavorable prognostic factor for bladder cancer.
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