NEDD4 Depletion Inhibits Hepatocellular Carcinoma Growth via Targeting PTEN
NEDD4 Depletion Inhibits Hepatocellular Carcinoma Growth via Targeting PTEN
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NEDD4 缺失通过靶向 PTEN 抑制肝细胞癌生长
DOI：
10.1159/000445667
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Xu, Wensheng
中科院分区：
文献类型：
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作者：
Hang, Xiaofeng;Zhu, Shanbang;Xu, Wensheng
背景/目的：神经前体细胞表达的发育下调基因4(NEDD4)在肿瘤细胞生长中起重要作用，但其在肝细胞癌中的作用尚不清楚。本研究旨在建立NEDD4作为预测肝细胞癌患者预后的生物标志物，并揭示NEDD4在肝癌细胞生长中的作用。方法：采用免疫组织化学方法检测219例肝细胞癌组织中NEDD4的表达。术后总生存期和复发时间通过单因素和多因素分析进行评估。确定NEDD4在肝癌细胞增殖和侵袭中的作用。结果：NEDD4低表达肿瘤患者平均累积生存期为64.9±6.5个月，高表达肿瘤患者平均累积生存时间为20.3±15.8个月。NEDD4的沉默抑制了Huh7细胞的增殖，改变了细胞骨架的组装，NEDD4的缺失似乎进一步抑制了细胞的迁移和侵袭。NEDD4沉默可能是导致PTEN(磷酸酶和张力蛋白同源)表达增加，进而导致STAT3、AKT和ERK1/2失活的一个可能的分子机制。结论：NEDD4可能参与了肝癌的进展，因此可能是肝癌治疗的潜在靶点。
Background/Aims: Neural precursor cell-expressed developmentally down-regulated gene 4 (NEDD4) plays an important role in tumor cell growth, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study is to establish NEDD4 as a prognostic biomarker by which the survival of HCC patients can be predicted and to reveal the role of NEDD4 in hepatocellular carcinoma cell growth. Methods: The expression of NEDD4 in 219 HCC specimens was assessed by immunohistochemistry. Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses. The roles of NEDD4 in hepatocellular carcinoma cell proliferation and invasion were determined. Results: The patients with low NEDD4 expression tumors had an average cumulative survival of 64.9 ± 6.5 months during follow-up while the patients with high NEDD4 expression tumors had an average cumulative survival of 20.3 ± 15.8 months. NEDD4 silencing inhibited Huh7 cell proliferation and altered cell cytoskeletal assembly, and NEDD4 depletion furthermore seemed to suppress cell migration and invasion. A possible molecular mechanism for the observed effects might be that NEDD4 silence led to an increase in PTEN (phosphatase and tensin homologue) expression, which in turn resulted in the inactivation of STAT3, AKT, and ERK1/2. Conclusion: Our findings indicate that NEDD4 may participate in the HCC progression and may therefore be a potential target for HCC therapy.