Abstract 3029: Role of eIF3a expression in cellular sensitivity to radiation treatment

Abstract

Abstract Translation initiation involving eukaryotic translation initiation factors (eIFs) is a crucial mechanism in controlling gene expression. eIF3a has been shown previously to regulate protein synthesis and cellular response to cisplatin treatment. Its expression has also been shown to negatively associate with prognosis. In this study, we tested a hypothesis that eIF3a regulates synthesis of DNA repair proteins, which in turn regulates cellular response to ionizing radiation (IR) treatments. We found that eIF3a overexpression sensitizes cellular response to IR while its knockdown causes resistance to IR. We also found that eIF3a over-expression increases IR-induced DNA damage and decreases Non-Homologous End Joining (NHEJ) repair activity by suppressing expression level of NHEJ repair proteins such as DNAPKcs. Consistently, eIF3a knockdown decreases IR-induced DNA damage and increases Non-Homologous End Joining (NHEJ) repair activity by enhancing expression level of NHEJ repair proteins. Together, we conclude that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating synthesis of DNA repair proteins and, thus, eIIF3a likely plays an important role in the outcome of cancer patients treated with DNA-damaging strategies. Note: This abstract was not presented at the meeting. Citation Format: Rima A. Tumia. Role of eIF3a expression in cellular sensitivity to radiation treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3029. doi:10.1158/1538-7445.AM2015-3029