miR-320 enhances the sensitivity of human colon cancer cells to chemoradiotherapy in vitro by targeting FOXM1

Biochem Biophys Res Commun. 2015 Feb 6;457(2):125-32. doi: 10.1016/j.bbrc.2014.11.039. Epub 2014 Nov 21.

Abstract

miR-320 expression level is found to be down-regulated in human colon cancer. To date, however, its underlying mechanisms in the chemo-resistance remain largely unknown. In this study, we demonstrated that ectopic expression of miR-320 led to inhibit HCT-116 cell proliferation, invasion and hypersensitivity to 5-Fu and Oxaliplatin. Also, knockdown of miR-320 reversed these effects in HT-29 cells. Furthermore, we identified an oncogene, FOXM1, as a direct target of miR-320. In addition, miR-320 could inactive the activity of Wnt/β-catenin pathway. Finally, we found that miR-320 and FOXM1 protein had a negative correlation in colon cancer tissues and adjacent normal tissues. These findings implied that miR-320-FOXM1 axis may overcome chemo-resistance of colon cancer cells and provide a new therapeutic target for the treatment of colon cancer.

Keywords: Chemo-resistance; Colon cancer; FOXM1; Wnt; miR-320.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Chemoradiotherapy*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Organoplatinum Compounds / pharmacology
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin

Substances

  • 3' Untranslated Regions
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • MIRN320 microRNA, human
  • MicroRNAs
  • Organoplatinum Compounds
  • Oxaliplatin
  • Fluorouracil