NRAGE is involved in homologous recombination repair to resist the DNA-damaging chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell survival in squamous esophageal tumorigenesis.

a neurotrophin receptor-interacting melanoma antigen-encoding gene homolog, is significantly increased in the nucleus of radioresistant esophageal tumor cell lines and is highly upregulated to promote cell proliferation in esophageal carcinomas (ECs). However, whether the overexpressed promotes cell growth by participating in DNA-damage response (DDR) is still unclear. Here we show that Nduanyu1648 is required for efficient double-strand breaks (DSBs) repair via homologous recombination repair (HRR) and downregulation of Nduanyu1648 greatly sensitizes EC cells to DNA-damaging agents both in vitro and in vivo. Moreover, Nduanyu1648 not only regulates the stability of DDR factors, RNF8 and BARD1, in a ubiquitin-proteolytic pathway, but also chaperons the interaction between BARD1 and RNF8 via their RING domains to form a novel ternary complex. Additionally, the expression of Nduanyu1648 is closely correlated with RNF8 and BARD1 in esophageal tumor tissues. In summary, our findings reveal a novel function of Nduanyu1648 that will help to guide personalized esophageal cancer treatments by targeting Nduanyu1648 to increase cell sensitivity to DNA-damaging therapeutics in the long run.

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