Expression of microRNA-133 inhibits epithelial-mesenchymal transition in lung cancer cells by directly targeting FOXQ1

Arch Bronconeumol. 2016 Oct;52(10):505-11. doi: 10.1016/j.arbres.2015.10.016. Epub 2016 Feb 5.
[Article in English, Spanish]

Abstract

Introduction: MicroRNA (miR) was implicated in the tumorigenesis of many types of cancer, but no study was conducted on the exact role of miR-133 in lung cancer.

Methods: We have identified miR-133 as a putative regulator of FOXQ1 expression, and investigated the potential involvement of miR-133 in the migration and invasion of lung cancer cells, as well as the underlying molecular mechanism.

Results: MiR-133 directly targeted and down-regulated FOXQ1 expression, which in turn reduced TGF-β level. MiR-133 was down-regulated in lung cancer cell lines A549 and HCC827, and its re-expression significantly inhibited the migration and invasion of the lung cancer cells. Further investigation revealed that this inhibition was caused by reversing the epithelial-mesenchymal transition, evidenced by miR-133 induced elevation of epithelial marker E-cadherin, and reduction of mesenchymal marker Vimentin.

Conclusions: Our study is the first to identify miR-133 as a biomarker for lung cancer. It functions to down-regulate FOXQ1, and inhibit epithelial-mesenchymal transition, which antagonizes lung cancer tumorigenesis. Therefore our data support the role of miR-133 as a potential molecular therapeutic tool in treating lung cancer.

Keywords: Cáncer de pulmón; Epithelial-mesenchymal transition; FOXQ1; Lung cancer; MicroARN-133; MicroRNA-133; TGF-β; Transición epitelio-mesenquimatosa.

MeSH terms

  • 3' Untranslated Regions
  • Antigens, CD
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cell Adhesion
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / physiology*
  • Forkhead Transcription Factors / biosynthesis*
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / physiology*
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Vimentin / biosynthesis
  • Vimentin / genetics

Substances

  • 3' Untranslated Regions
  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • FOXQ1 protein, human
  • Forkhead Transcription Factors
  • MIRN133 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Transforming Growth Factor beta
  • Vimentin