Down-regulation of miR-129-5p via the Twist1-Snail feedback loop stimulates the epithelial-mesenchymal transition and is associated with poor prognosis in breast cancer

// Yue Yu 1, 2, 3 , Ying Zhao 1, 2, 3 , Xiao-Hu Sun 1, 2, 3 , Jie Ge 1, 2, 3 , Bin Zhang 1, 2, 3 , Xin Wang 1, 2, 3 , Xu-Chen Cao 1, 2, 3 1 The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China 3 Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China Correspondence to: Xu-Chen Cao, e-mail: caoxuchen@tmu.edu.cn Keywords: miR-129-5p, Twist1, Snail, EMT, breast cancer progression Received: May 20, 2015 Accepted: September 25, 2015 Published: October 07, 2015 ABSTRACT The epithelial to mesenchymal transition (EMT) plays a pivotal role in breast cancer progression. We found that overexpression of miR-129-5p reversed EMT, whereas depletion of miR-129-5p induced EMT in breast cancer cells. We demonstrated that Twist1 is a direct target of miR-129-5p. Both Twist1 and Snail transcriptionally suppressed miR-129-5p expression. Levels of miR-129-5p were low in breast cancer tissues. miR-129-5p down-regulation correlated with advanced clinical stage and poor prognosis in patients with breast cancer. miR-129-5p expression negatively correlated with Twist1 and Snail expression. Thus, miR-129-5p down-regulation fosters EMT in breast cancer by increasing Twist1-Snail and activating a negative feedback loop.