miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer

Oncol Rep. 2015 May;33(5):2592-8. doi: 10.3892/or.2015.3833. Epub 2015 Mar 4.


Forkhead box F2 transcription factor (FoxF2) has been described to promote organ development, extracellular matrix (ECM) synthesis and epithelial-mesenchymal interaction. Although recent studies reported decreased FoxF2 expression in several types of cancers, indicating its potential role in carcinogenesis, the mechanistic role of FoxF2 is yet to be explored. MicroRNAs (miRNAs) are strongly implicated in carcinogenesis. The oncogenetic properties of miR-182 have been described in multiple cancers. In the present study, we aimed to investigate the role of miR-182 in colorectal cancer (CRC) and identify the regulation of FoxF2 by miR-182. Bioinformatic analyses on gene expression profiling datasets showed decreased FoxF2 expression in colorectal adenomas, primary tumors compared to normal colon epithelial and a negative association between FoxF2 and β-catenin expression. Restoration of FoxF2 in CRC cells suppressed β-catenin expression and simultaneously inhibited cell growth and invasion. Furthermore, we observed that miR-182 was aberrantly upregulated in CRC. Knockdown of miR-182 in CRC cells impeded cell growth and invasion. The direct binding of miR-182 to the 3' untranslated region (3'UTR) of FoxF2 mRNA was confirmed using a luciferase reporter gene assay. Importantly, elevated FoxF2 expression was observed in miR-182-knockdown cells with a simultaneous reduction in β-catenin. In conclusion, the present study describes a potential mechanism underlying an miR-182/FoxF2 link contributing to CRC development. miR-182-induced downregulation of FoxF2 partly accounts for increased activity of β-catenin signaling. Inhibition of miR-182 represents a potential strategy against CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Down-Regulation / genetics
  • Epithelial Cells / metabolism
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • RNA, Messenger / genetics
  • Transcription Factors / genetics*
  • Up-Regulation / genetics
  • beta Catenin / genetics


  • 3' Untranslated Regions
  • FOXF2 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs
  • Mirn182 microRNA, human
  • RNA, Messenger
  • Transcription Factors
  • beta Catenin