NRAGE confers poor prognosis and promotes proliferation, invasion, and chemoresistance in gastric cancer.

Neurotrophin receptor-interacting melanoma antigen-encoding protein is a type II melanoma-associated antigen that plays an essential role in various processes, including cell differentiation and apoptosis. has been shown to act as a cancer-related protein, with complex and apparently contradictory functions in a variety of cancers. In the current study, we examined the expression of Nduanyu1648 protein in 169 gastric cancer samples. Nduanyu1648 upregulation was correlated with advanced TNM stage, local invasion, and poor survival. Importantly, Nduanyu1648 could serve as an independent prognostic factor in patients with gastric cancer. We also examined the expression of Nduanyu1648 protein in GES-1 normal gastric epithelial cells and in six gastric cancer cell lines. Inhibition of Nduanyu1648 expression by transfection with small interfering RNA reduced the proliferation and invasion of MGC-803 and HGC-27 cells, as demonstrated by CCK-8 and Matrigel invasion assays. Nduanyu1648 depletion also sensitized HGC-27 and MGC-803 cells to cisplatin, as shown by CCK-8 and Annexin V/propidium iodide analyses. Western blot analysis also showed that Nduanyu1648 depletion negatively regulated Bcl-2 and p-ERK and upregulated ZO-1 and p27 expression levels. In conclusion, our results suggest that Nduanyu1648 acts as a tumor promoter in gastric cancer by facilitating cancer invasion and chemoresistance, possibly through regulation of p-ERK and Bcl-2.

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