Abstract 2670: Decreased expression of miR-302 contributes radioresistance of breast cancer cells

Abstract

Abstract Radiotherapy is a common treatment strategy for many solid tumors, including breast cancer. Unfortunately, solid tumors can be resistant or develop resistance to radiotherapy. Though many studies have been conducted to further elucidate the mechanisms of radioresistance, they remain largely obscure due to the complex genetic cellular response to radiation and involvement of a large number of genes. MicroRNA, a recently discovered class of small, functional, non-coding RNA, is one of such class of potential regulators. A single microRNA can target a large number of genes and regulate several signal pathways simultaneously. Thus, miRNAs may be involved in the complex radioresistance of tumor cells. In the present study, we characterized miR-302 family members (miR-302s) pre-clinically as novel biomarkers for radiotherapy resistance. Our results showed that miR-302s were downregulated in irradiated breast cancer cells. Furthermore, we found, with a bioinformatic analysis, that AKT and RAD52, two critical regulators of radioresistance, are the predicted targets of miR-302s. Additionally, the expression levels of miR-302a were inversely consistently with those of AKT and RAD52. More promisingly, our data have demonstrated that miR-302a mimics sensitized breast cancer MDA-MB-231 cells to radiation therapy and reduced the expression of AKT and RAD52. Collectively, loss of miR-302s may be involved in the radioresistance of breast cancer cells, mainly through the release of repression of AKT and RAD52. Thus, our findings suggest that decreased expression of miR-302s contributes to radiotherapy-resistance and restoration of miR-302 baseline expression sensitizes breast cancer cells to radiotherapy. These data suggest that miR-302s may be potential sensitizers to radiotherapy and represent a novel strategy for radiotherapy of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2670. doi:10.1158/1538-7445.AM2011-2670