PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth

// Wei Xiang 1, 2 , Xinchao Wu 1 , Chao Huang 1 , Miao Wang 1 , Xian Zhao 1 , Gang Luo 1 , Yawei Li 1 , Guosong Jiang 1 , Xingyuan Xiao 1 , Fuqing Zeng 1 1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, PR China 2 Department of Urology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, PR China Correspondence to: Xingyuan Xiao, email: xiaoxingyuan2007@gmail.com Fuqing Zeng, email: fuqingzengpro@126.com Keywords: bladder cancer, PTTG1, miR-146a-3p Received: April 15, 2016      Accepted: November 11, 2016      Published: November 22, 2016 ABSTRACT Pituitary tumor-transforming gene 1 (PTTG1) is identified as an oncogene, and overexpresses in many tumors. However, the role of PTTG1 in bladder cancer (BC) hasn’t yet been characterized well. In this study, we showed the expression of PTTG1 mRNA and protein were both significantly increased in BC tissues and cells. The PTTG1 protein levels were positive correlated with increased tumor size, tumor–node–metastasis (TNM) stage, lymphatic invasion and distant metastasis of BC. PTTG1 knockdown dramatically suppressed the migration, invasion, metastasis and growth, and induced senescence and cell-cycle arrest at G0/G1 phase of BC cells. We further identified PTTG1 was the direct target of miR-146a-3p through using target prediction algorithms and luciferase reporter assay. miR-146a-3p was low expressed and negatively correlated with PTTG1 levels in BC tissues and cells. miR-146a-3p overexpression inhibited migration, invasion, metastasis and growth, and induced senescence of BC cells. Rescue experiment suggested ectopic expression of miR-146a-3p and PTTG1 suppressed migration, invasion and induced cell cycle arrest and senescence of BC cells compared to PTTG1 overexpression, confirming miR-146a-3p inhibited BC progression by targeting PTTG1. In summary, our study found miR-146a-3p/PTTG1 axis regulated BC migration, invasion, metastasis and growth, and might be a targets for BC therapy.