miR-204 functions as a tumor suppressor by regulating SIX1 in NSCLC

FEBS Lett. 2014 Oct 16;588(20):3703-12. doi: 10.1016/j.febslet.2014.08.016. Epub 2014 Aug 23.

Abstract

The involvement of miR-204 in lung cancer development is unclear. In our study, we analyzed the expression of miR-204 in tumor- and adjacent-tissue samples from 141 patients with non-small cell lung cancer (NSCLC). MiR-204 expression was decreased in tumor samples compared with non-cancerous tissue-derived controls. Moreover, miR-204 expression negatively correlated with homeobox protein SIX1 expression, tumor size and metastasis. MiR-204 silencing in miR-204-positive NSCLC cell lines promoted cell invasion and proliferation. Concomitantly, MiR-204 overexpression resulted in reduced cell proliferation and invasion, upregulated E-cadherin and downregulated N-cadherin and Vimentin expression. SIX1 was identified as a potential target of miR-204, and SIX1 silencing partially compromised the invasive and proliferative capacity of miR-204-deficient cells. Thus, miR-204 may be involved in the NSCLC development.

Keywords: Epithelial-to-mesenchymal transition; Invasion; Non-small cell lung cancer; Proliferation; SIX1; miR-204.

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Protein Binding

Substances

  • 3' Untranslated Regions
  • Homeodomain Proteins
  • MIRN204 microRNA, human
  • MicroRNAs
  • SIX1 protein, human