MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b

J Exp Clin Cancer Res. 2013 May 29;32(1):33. doi: 10.1186/1756-9966-32-33.

Abstract

Background: The metastasis-associated gene 1 (MTA1) has been identified as one critical regulator of tumor metastasis. Previously, we identified miR-125b as a downregualted miRNA in non-small cell lung cancer (NSCLC) cell line upon MTA1 depletion. However, the role of miR-125b and MTA1 in the regulation of NSCLC metastasis remains unclear.

Methods: Stable MTA1 knockdown NSCLC cell lines 95D and SPC-A-1 were established by transfection with MTA1 shRNA. The effects of MTA1 depletion on the expression of miR-125b and cell migration and invasion were examined by real-time PCR, wound healing and matrigel invasion assay.

Results: MTA1 knockdown led to the upregulation of miR-125b level in NSCLC cells. Furthermore, MTA1 knockdown reduced while miR-125b inhibitor enhanced cell migration and invasion of NSCLC cells. Notably, miR-125b inhibitor antagonized MTA1 siRNA induced inhibition of cell migration and invasion.

Conclusion: MTA1 and miR-125b have antagonistic effects on the migration and invasion of NSCLC cells. The newly identified MTA1-miR-125b axis will help further elucidate the molecular mechanism of NSCLC progression and suggest that ectopic expression of miR-125b is a potentially new therapeutic regimen against NSCLC metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Trans-Activators

Substances

  • MIRN125 microRNA, human
  • MicroRNAs
  • MTA1 protein, human
  • Repressor Proteins
  • Trans-Activators
  • Histone Deacetylases