MiR-23a promotes TGF-β1-induced EMT and tumor metastasis in breast cancer cells by directly targeting CDH1 and activating Wnt/β-catenin signaling

// Fei Ma 1 , Wenjie Li 1 , Chunxiao Liu 1 , Wei Li 1 , Haining Yu 1 , Bo Lei 1 , Yanlv Ren 1 , Zhigao Li 1 , Da Pang 1, 2 and Cheng Qian 1, 2 1 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China 2 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China Correspondence to: Cheng Qian, email: qiancheng@ems.hrbmu.edu.cn Da Pang, email: Pangdasir@163.com Keywords: miR-23a, TGF-β1, R-SBE, CDH1, Wnt/β-catenin Received: January 21, 2017      Accepted: May 10, 2017      Published: June 09, 2017 ABSTRACT TGF-β1-induced epithelial-mesenchymal transition (EMT) has been proved to be associated with metastasis of breast cancer cells. We attempted to detect a novel mechanism that microRNAs mediated the TGF-β1-induced EMT in the process of breast cancer metastasis. Here we reported that the expression of miR-23a was higher in breast cancer cells with high metastasis ability and patients with lymph node metastasis and the treatment of TGF-β1 significantly upregulated the expression of miR-23a in breast cancer cells. We found that miR-23a was upregulated by TGF-β1 post-transcriptionally and Smads directly bound the RNA Smad binding element (R-SBE) of miR-23a. Functional studies showed that inhibition of miR-23a suppressed the TGF-β1-induced EMT, migration, invasion and metastasis of breast cancer both in vitro and in vivo . In addition, we determined that miR-23a directly targeted and suppressed CDH1, one important gene in EMT phenomenon. Notably, Wnt/β-catenin signaling was activated by the suppression of CDH1 in the miR-23a mediated process of TGF-β1-induced EMT and tumor invasion. These results demonstrate that miR-23a promotes TGF-β1-induced tumor metastasis in breast cancer by targeting CDH1 and activating Wnt/β-catenin signaling. Taken together, our results indicate a novel regulatory mechanism of TGF-β1-induced EMT and suggest that miR-23a might be a potential target in breast cancer therapy.