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MicroRNA-302 Replacement Therapy Sensitizes Breast Cancer Cells to Ionizing Radiation

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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.

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Abbreviations

AKT:

protein kinase B

Gy:

gray

miRNA:

microRNA

RAD52:

a protein, encoded by the RAD52 gene, important for DNA double-strand break repair and homologous recombination

RT-PCR:

reverse transcription polymerase chain reaction.

siRNA:

small interfering RNA

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was financially supported by the Department of Defense Breast Cancer Program Concept Award (BC052118) to ZL as well as a Research Grant from NIH NCI (1R01CA109366) to HS. We acknowledge Dr. Ya Wang for stimulating discussions. We thank Hongyan Wang and Ping Wang for technical assistance. The authors thank Jessica Paulishen for proof-reading.

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Authors and Affiliations

  1. Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia, 30322, USA

    Zhongxing Liang, Jeffrey Ahn, Donna Guo, John R. Votaw & Hyunsuk Shim

  2. Winship Cancer Institute, Emory University, Atlanta, Georgia, 30322, USA

    Zhongxing Liang & Hyunsuk Shim

Authors
  1. Zhongxing Liang
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  2. Jeffrey Ahn
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  3. Donna Guo
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  4. John R. Votaw
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  5. Hyunsuk Shim
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Correspondence to Zhongxing Liang or Hyunsuk Shim.

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Liang, Z., Ahn, J., Guo, D. et al. MicroRNA-302 Replacement Therapy Sensitizes Breast Cancer Cells to Ionizing Radiation. Pharm Res 30, 1008–1016 (2013). https://doi.org/10.1007/s11095-012-0936-9

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  • DOI: https://doi.org/10.1007/s11095-012-0936-9

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