Mir-23a Promotes Tgf-Beta 1-Induced Emt And Tumor Metastasis In Breast Cancer Cells By Directly Targeting Cdh1 And Activating Wnt/Beta-Catenin Signaling

TGF-beta 1-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-beta 1-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-beta 1 significantly upregulated the expression of miR-23a in breast cancer cells. We found that miR-23a was upregulated by TGF-beta 1 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-beta 1-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/beta-catenin signaling was activated by the suppression of CDH1 in the miR-23a mediated process of TGF-beta 1-induced EMT and tumor invasion. These results demonstrate that miR-23a promotes TGF-beta 1-induced tumor metastasis in breast cancer by targeting CDH1 and activating Wnt/beta-catenin signaling. Taken together, our results indicate a novel regulatory mechanism of TGF-beta 1-induced EMT and suggest that miR-23a might be a potential target in breast cancer therapy.