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

NKD1 correlates with a poor prognosis and inhibits cell proliferation by inducing p53 expression in hepatocellular carcinoma
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NKD1 与肝细胞癌的不良预后相关,并通过诱导 p53 表达抑制细胞增殖

DOI:
10.1007/s13277-016-5173-0
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发表时间:
2016-08
期刊:
影响因子:
--
通讯作者:
Wang Xiaomin
Wang Xiaomin
中科院分区:
--
文献类型:
--
作者:
Zhang Sheng;Li Jie;Wang Xiaomin

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裸角质层1(NKD 1),Wnt信号通路的负调控因子,在许多类型的恶性肿瘤中异常表达。然而,NKD 1在肝细胞癌(HCC)细胞增殖中的作用和机制及其与HCC患者预后的关系尚不清楚。本研究应用实时荧光定量PCR技术检测了60例肝癌组织及相应癌旁组织中NKD 1 mRNA的表达情况,发现NKD 1 mRNA在肝癌组织中的表达相对低于癌旁组织,且与肿瘤大小呈负相关。Kaplan-Meier生存曲线显示,NKD 1表达较低的患者术后预后较差。此外,NKD 1的过表达抑制肝癌细胞的增殖能力,而敲低NKD 1则具有相反的效果。体内试验表明,注射SMMC-7721 +对照细胞的小鼠比注射SMMC-7721 + NKD 1的小鼠具有更大的肿瘤结节。机制研究表明NKD 1通过诱导p53表达抑制肝癌细胞增殖。综上所述,我们的研究表明,NKD 1 mRNA的表达在肝癌组织中下调,并与预后不良相关。NKD 1通过诱导p53表达抑制肝癌细胞增殖。
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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