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

• Authors: Zhongxing Liang, Emory University; Jeffrey Ahn, Emory University; Donna Guo, Emory University; John R Votaw, Emory University; Hyunsuk Shim, Emory University
• Journal Title: Pharmaceutical Research
• Volume: Volume 30, Number 4
• Publisher: American Association of Pharmaceutical Scientists | 2013-04, Pages 1008-1016
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s11095-012-0936-9
• Subjects: Health Sciences, Oncology; Biology, Radiation; Health Sciences, Medicine and Surgery
• Keywords: microRNA; radioresistance; AKT; breast cancer

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.