Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer

// Shiqi Li 1, * , Yi Zhu 1, * , Zhen Liang 1 , Xiao Wang 1 , Shuai Meng 1 , Xin Xu 1 , Xianglai Xu 1 , Jian Wu 1 , Alin Ji 1 , Zhenghui Hu 1 , Yiwei Lin 1 , Hong Chen 1 , Yeqing Mao 1 , Wei Wang 1 , Xiangyi Zheng 1 , Ben Liu 1 , Liping Xie 1 1 Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, PR China * These authors contributed equally to this work and are Co-first authors Correspondence to: Ben Liu, email: drliuben@sina.com Liping Xie, email: xielp@zju.edu.cn Keywords: bladder cancer, microRNA-877-3p, p16, RNA activation Received: January 17, 2016 Accepted: June 29, 2016 Published: July 13, 2016 ABSTRACT Despite the recent studies which have shown that microRNA (miRNA) negatively regulates gene expression by silencing the expression of target genes, here we reported the new evidence of microRNA-mediated gene activation by targeting specific promoter sites. We identified a miR-877-3p binding site on the promoter site of tumor suppressor gene p16 which alters frequently in bladder cancer. Enforced expression of miR-877-3p could increase the expression of p16, which inhibit the proliferation and tumorigenicity of bladder cancer through cell cycle G1-phase arrest. Further evidences confirmed that the correlation between p16 activation and miR-877-3p was due to the direct binding. These findings demonstrate the anti-tumor function of miR-877-3p in bladder cancer cells and reveal a new pattern of miRNA involved gene regulation.