Abstract 1106: Targeting both non-coding and coding sequences with small RNA efficiently knocks down DNA repair genes and radiosensitizes human tumor cells

Abstract

Abstract During radiotherapy, human tumor cell death is mainly caused by ionizing radiation (IR)-induced DNA double strand breaks (DSBs). In general, human cells use two pathways: homologous recombination repair (HRR) and non-homologous end-joining (NHEJ), to repair DNA DSBs. However, in many cases, human tumors are resistant to IR due to the abnormal up-regulation of DNA DSB repair genes. Previously it was reported that using a siRNA approach could knock down the DNA DSB repair genes and sensitized the tumor cells to IR, however, the levels of knock down using a siRNA approach alone is limited. Here, we developed a novel combined approach using an artificial microRNA (amiR) to target the 3′-untranlated region (UTR) of the DNA DSB repair gene, XRCC2 (a HRR factor) or XRCC4 (a NHEJ factor), and the siRNA to target the coding region of the gene in different human tumor cell lines. Our results indicate that the combined approach is much more efficient than the amiR or siRNA approach alone in knocking down the targeted gene and sensitizing human tumor cells to IR-induced killing. The amiR decreased the targeted gene through reducing the mRNA stability and blocking the translation. These results demonstrate that the combined approach could be used for many different purposes to knock down genes in different cell lines, especially genes that are difficult to knock down using amiR or siRNA alone. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1106. doi:1538-7445.AM2012-1106