Down-regulation of miR-26 plays essential roles in TGFβ-induced EMT.

Epithelial mesenchymal transformation (EMT) plays fundamental roles in tumor metastasis. MiRNAs function as powerful regulators of EMT. The function and mechanism of miRNAs in EMT of lung cancers remains to be elucidated. Here, we explored the roles and mechanisms of miR-26a in EMT. A cellular EMT model was firstly established by TGFβ incubation with A549 cells. Compared with control, the expression of miR-26a was down-regulated by 60% in EMT model. Down-regulation of miR-26a was further revealed to increase the expression of mesenchymal markers (N-cadherin, Vimentin, a-Sma and Twist1) and decrease epithelial marker (E-cadherin). Consistently, over-expression of miR-26a partially attenuated the regulatory activity of TGFβ on the expression of EMT markers in A549 cells. These results indicate that down-regulation of miR-26a plays essential functions in TGFβ-induced EMT. Furthermore, Smad1 and Smad4 were predicted to be potential targets of miR-26a. Over-expression of miR-26a suppressed the luciferase activity of Renilla whose 3' UTR harbors the sequences of Smad1 or Smad4 that might bind to miR-26a, indicating that miR-26a can directly bind to 3' UTR of Smad1 and Smad4. Accordingly, the protein levels of SMAD1 and SMAD4 were significantly suppressed by miR-26a over-expression in A549 cells. Interestingly, the suppressing effects of miR-26a on EMT were totally rescued by over-expression of SMAD1 and SMAD4 in TGFβ-treated A549 cells. Collectively, down-regulation of miR-26a plays essential roles in TGFβ-induced EMT, which might provide important implications for the therapeutics of lung cancers. This article is protected by copyright. All rights reserved.