MicroRNA-302 replacement therapy sensitizes breast cancer cells to ionizing radiation

Pharm Res. 2013 Apr;30(4):1008-16. doi: 10.1007/s11095-012-0936-9. Epub 2012 Nov 27.

Abstract

Purpose: Solid tumors can be resistant or develop resistance to radiotherapy. The purpose of this study is to explore whether microRNA-302 is involved in radioresistance and can be exploited as a sensitizer to enhance sensitivity of breast cancer cells to radiation therapy.

Methods: MiR-302 expression levels in radioresistant cell lines were analyzed in comparison with their parent cell lines. Furthermore, we investigated whether enforced expression of miR-302 sensitized radioresistant breast cancer cells to ionizing radiation in vitro and in vivo.

Results: MiR-302 was downregulated in irradiated breast cancer cells. Additionally, the expression levels of miR-302a were inversely correlated with those of AKT1 and RAD52, two critical regulators of radioresistance. More promisingly, miR-302a sensitized radioresistant breast cancer cells to radiation therapy in vitro and in vivo and reduced the expression of AKT1 and RAD52.

Conclusion: Our findings demonstrated that decreased expression of miR-302 confers radioresistance and restoration of miR-302 baseline expression sensitizes breast cancer cells to radiotherapy. These data suggest that miR-302 is a potential sensitizer to radiotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast / metabolism
  • Breast / pathology
  • Breast / radiation effects*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Rad52 DNA Repair and Recombination Protein / genetics
  • Radiation Tolerance

Substances

  • MIRN302A microRNA, human
  • MicroRNAs
  • RAD52 protein, human
  • Rad52 DNA Repair and Recombination Protein
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt