Activating enhancer-binding protein-2α induces cyclooxygenase-2 expression and promotes nasopharyngeal carcinoma growth

// Dingbo Shi 1,* , Xiangsheng Xiao 1,* , Yun Tian 1,* , Lijun Qin 3 , Fangyun Xie 1 , Rui Sun 1 , Jingshu Wang 1 , Wenbin Li 1 , Tianze Liu 1 , Yao Xiao 2 , Wendan Yu 2 , Wei Guo 2 , Yuqing Xiong 1 , Huijuan Qiu 1 , Tiebang Kang 1 , Wenlin Huang 1,4 , Chong Zhao 1 and Wuguo Deng 1,4 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 2 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China 3 Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 4 State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China * These authors contributed equally to this manuscript Correspondence: Chong Zhao, email: // Wuguo Deng, email: // Keywords : AP-2α, COX-2, p300, nasopharyngeal carcinoma Received : November 07, 2014 Accepted : December 26, 2014 Published : December 31, 2014 Abstract Activating enhancer-binding protein-2α (AP-2α) regulates the expression of many cancer-related genes. Here, we demonstrated a novel mechanism by which AP-2α up-regulated cyclooxygenase-2 (COX-2) expression to promote the growth of nasopharyngeal carcinomas (NPCs). High expression of AP-2α in NPC cell lines and tumor tissues from NPC patients was detected and significantly correlated with COX-2 expression. Overexpression of AP-2α and COX-2 in tumor tissues was associated with advanced tumor stage, clinical progression, and short survival of patients with NPCs. Knockdown of AP-2α by siRNA markedly inhibited COX-2 expression and PGE2 production in NPC cells. Exogenous expression of AP-2α up-regulated the COX-2 and PGE2. Knockdown of AP-2α also significantly suppressed cell proliferation in NPC cells in vitro and tumor growth in a NPC xenograft mouse model. Moreover, we found that p300 played an important role in the AP-2α/COX-2 pathway. AP-2α could co-localize and interact with p300 in NPC cells. Overexpression of the p300, but not its histone acetyltransferase (HAT) domain deletion mutant, promoted the acetylation of AP-2α and its binding on the COX-2 promoter, thereby up-regulated COX-2 expression. Our results indicate that AP-2α activates COX-2 expression to promote NPC growth and suggest that the AP-2α/COX-2 signaling is a potential therapeutic target for NPC treatment.