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
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Yue Yu1,2,3, Ying Zhao1,2,3, Xiao-Hu Sun1,2,3, Jie Ge1,2,3, Bin Zhang1,2,3, Xin Wang1,2,3, Xu-Chen Cao1,2,3
1The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China
2Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
3Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China
Xu-Chen Cao, e-mail: [email protected]
Keywords: miR-129-5p, Twist1, Snail, EMT, breast cancer progression
Received: May 20, 2015 Accepted: September 25, 2015 Published: October 07, 2015
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.
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