Knockdown of NRAGE Impairs Homologous Recombination Repair and Sensitizes Hepatoblastoma Cells to Ionizing Radiation.

(neurotrophin receptor-interacting melanoma antigen-encoding gene homolog) has a complex role and regulates cell growth in different tumor cells. Although Nduanyu1648 was been discovered for more than 10 years ago, the function of Nduanyu1648 in hepatoblastoma (HB) cells is currently unknown. The expression of Nduanyu1648 was detected by reverse transcription-quantitative polymerase chain reaction assay or western blotting assay. Cellular apoptosis was analyzed to estimate the effect of Nduanyu1648 under radiation. The ability of clonogenic capacity was evaluated to confirm the influence of proliferation for Nduanyu1648 by radiation. The immunofluorescence assay was used to further study the expression of Nduanyu1648 under radiation. A nude mouse tumor xenograft model was constructed to confirm the effect of Nduanyu1648 deficiency under radiation conditions in vivo. The authors determined that deletion of Nduanyu1648 significantly inhibited HB cell proliferation in vitro and in vivo, and Nduanyu1648 knockdown apparently sensitized HB cells to ionizing radiation (IR). Further mechanistic studies revealed that Nduanyu1648 plays a critical role in homologous recombination by inhibiting the expression of RNF8 (ring finger protein 8) and BARD1 (BRCA1 associated RING domain 1) and the recruitment of RAD51. The authors demonstrated that downregulation of Nduanyu1648 sensitizes HB cell lines to IR in vitro and in vivo. It provides a promising therapeutic strategy for HB patients by specifically targeting

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