NKD1 correlates with a poor prognosis and inhibits cell proliferation by inducing p53 expression in hepatocellular carcinoma

Abstract

Naked cuticle 1 (NKD1), a negative regulator of the Wnt signaling pathway, is abnormally expressed in many types of malignant tumors. Yet the role and mechanism of NKD1 in hepatocellular carcinoma (HCC) cell proliferation and its relationship with HCC patients' prognosis have been poorly characterized. In the present study, real-time polymerase chain reaction (PCR) was used to examine the mRNA expression patterns of NKD1 in the tissues of 60 patients with HCC and corresponding adjacent non-tumor tissues and found that NKD1 mRNA expression in HCC tissues was relatively lower than that in non-tumor tissues and negatively correlated with tumor size. Kaplan–Meier survival curves uncovered that patients with lower NKD1 expression had a poorer post-operative prognosis than those with higher expression. In addition, over-expression of NKD1 inhibited the HCC cell proliferation ability, whereas knockdown of NKD1 had the opposite effect. In vivo assays showed that mice injected with SMMC-7721 + control cells had bigger tumor nodules than those injected with SMMC-7721 + NKD1. Mechanism studies demonstrated that NKD1 repressed HCC cell proliferation by inducing p53 expression. Taken together, our study revealed that NKD1 mRNA expression was downregulated in HCC tissues and correlated with a poor prognosis. NKD1 inhibited HCC cell proliferation by inducing p53 expression.

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