MicroRNA-26b suppresses the metastasis of non-small cell lung cancer by targeting MIEN1 via NF-κB/MMP-9/VEGF pathways

Biochem Biophys Res Commun. 2016 Apr 8;472(3):465-70. doi: 10.1016/j.bbrc.2016.01.163. Epub 2016 Jan 28.


MicroRNAs (miRNAs) are involved in tumor initiation and progression. MiR-26b was reported to be significantly downregulated in non-small cell lung cancer (NSCLC). However, the underlying mechanisms of miR-26b involvement in the development and progression of NSCLC remains poorly understood. In the present study, we report that miR-26b suppresses cell metastasis in NSCLC through targeting migration and invasion enhancer 1 (MIEN1). We found that miR-26b was significantly downregulated and MIEN1 was significantly upregulated in both NSCLC tissues and cells lines. The expression levels of miR-26b were negatively related to those of MIEN1 mRNA in clinical NSCLC tissues. Furthermore, MIEN1 was confirmed to be a direct target of miR-26b by dual-luciferase reporter assay and MIEN1 expression was downregulated by miR-26b in NSCLC cells. In terms of function, transwell and wound healing assays demonstrated that the miR-26b remarkably inhibited invasion and migration of NSCLC cells, which was simulated by siRNA knockdown of MIEN1 and reversed by pcDNA/MIEN1 overexpression of MIEN1. Finally, we found that miR-26b could regulate NF-κB/MMP-9/VEGF pathway in NSCLC cells. In conclusion, this study revealed that miR-26b suppresses NSCLC metastasis by targeting MIEN1 via NF-κB/MMP-9/VEGF pathways, implicating a potential prognostic biomarker and therapeutic target for NSCLC treatment.

Keywords: MIEN1; Metastasis; MiR-26b; NF-κB/MMP-9/VEGF pathways; NSCLC.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism


  • Intracellular Signaling Peptides and Proteins
  • MIEN1 protein, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Neoplasm Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MMP9 protein, human
  • Matrix Metalloproteinase 9