Repression of Smad4 by miR‑205 moderates TGF-β-induced epithelial-mesenchymal transition in A549 cell lines

Int J Oncol. 2016 Aug;49(2):700-8. doi: 10.3892/ijo.2016.3547. Epub 2016 May 31.


The TGF-β/Smad signaling pathway plays important roles in cancer cell proliferation, apoptosis, differentiation, angiogenesis and epithelial-mesenchymal transition (EMT), which is the key event in the early stages of cancer metastasis and enhances the capability of cell migration and invasion. Smad4 acts as the only Co-Smad of TGF/Smad signaling pathway and plays the key role in TGF-β-mediated EMT. Nevertheless, the mRNA regulation mechanisms of Smad4 in human non-small cell lung cancer (NSCLC) remains largely unclear. Computational algorithms predicted that the 3'-UTR of Smad4 is a target of miR‑205. Here, we validated that miR‑205 could directly bind to 3'-UTR of Smad4 by luciferase assays. Moreover, we investigated the functional roles of miR‑205 and its molecular link to Smad4 in lung cancer cells. In this study, we confirmed that overexpression of miR‑205 suppressed the expression of Smad4, in turn, weakened the TGF-β/Smad signaling pathway and inhibited TGF-β/Smad4-induced EMT, invasion and migration ultimately. Furthermore, this study shows that miR‑205 can serve as a promising therapeutic target of highly aggressive NSCLC.

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Protein Binding
  • Signal Transduction / genetics
  • Smad4 Protein / antagonists & inhibitors
  • Smad4 Protein / biosynthesis
  • Smad4 Protein / genetics*
  • Transforming Growth Factor beta / genetics*


  • 3' Untranslated Regions
  • MIRN205 microRNA, human
  • MicroRNAs
  • SMAD4 protein, human
  • Smad4 Protein
  • Transforming Growth Factor beta