MiR-185 enhances radiosensitivity of colorectal cancer cells by targeting IGF1R and IGF2

Biomed Pharmacother. 2018 Oct:106:763-769. doi: 10.1016/j.biopha.2018.07.002. Epub 2018 Jul 11.

Abstract

Objective: Radioresistance is a significant obstacle for effective treatment of colorectal cancer (CRC). Recent studies have indicated that miR-185 inhibits proliferation, survival, and invasion of CRC; however, the role of this miRNA in radioresistance of CRC has not been identified yet. The aim of this study is to investigate the role of miR-185 in radiosensitivity of CRC.

Methods: After transfecting the cells with mimic miR-185, expressions of IGF1R and IGF2 were evaluated by real-time PCR and western blot. The radiation response of transfected cells was also examined by colony forming assay. Sub-G1 fraction analysis through flow cytometry and caspase 3 activity was used to evaluate apoptosis.

Results: The results of real-time PCR and western blot indicated that IGF1R and IGF2 are downregulated in the transfected cells. Colony forming assay revealed that transfected cells were more radiosensitive than other cells. On the other hand,following irradiation the rate of apoptosis was significantly higher in the transfected cells than in the other cells.

Conclusion: In summary, our study is the first to show that upregulation of miR-185 enhances the sensitivity of CRC cells to ionizing radiation. miR-185 may act as a novel biomarker of radioresistance and may clinically enhance the radiation response of CRC.

Keywords: Colorectal neoplasms; IGF1R; IGF2; MiR-185; Radioresistance.

MeSH terms

  • Apoptosis / radiation effects
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / radiation effects
  • Cell Proliferation / radiation effects
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / radiotherapy*
  • Dose-Response Relationship, Radiation
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Interaction Maps
  • Radiation Tolerance* / genetics
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / genetics
  • Receptors, Somatomedin / metabolism*
  • Signal Transduction / radiation effects
  • Time Factors

Substances

  • IGF1R protein, human
  • IGF2 protein, human
  • MIRN185 microRNA, human
  • MicroRNAs
  • Receptors, Somatomedin
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1
  • CASP3 protein, human
  • Caspase 3