Spermine oxidase is upregulated and promotes tumor growth in hepatocellular carcinoma
Spermine oxidase is upregulated and promotes tumor growth in hepatocellular carcinoma
复制标题
精胺氧化酶上调并促进肝细胞癌中的肿瘤生长。
DOI：
10.1111/hepr.13206
复制
发表时间：
2018-11-01
影响因子：
4.2
通讯作者：
Dong, Ling
中科院分区：
文献类型：
--
作者：
Hu, Tingting;Sun, Dalong;Dong, Ling
目的方法 多胺分解代谢酶、精胺氧化酶 (SMOX) 在慢性炎症条件下表达上调，并与各种癌症中活性氧的增加和 DNA 损伤有关。本研究旨在探讨SMOX在肝细胞癌（HCC）中的表达模式和生物学功能。我们采用实时定量聚合酶链反应、蛋白质印迹和免疫组织化学方法检测了 4 个 HCC 细胞系和 120 个 HCC 临床样本中 SMOX 的表达，并分析了 SMOX 的临床意义。在体外和体内检测了 SMOX 对 HCC 细胞的生物学功能。结果结论结果显示SMOX在HCC细胞系和临床HCC组织中过表达。此外，正常肝脏、慢性肝炎和肝癌组织中SMOX表达水平逐渐升高。 SMOX 表达增加与 HCC 不良临床特征相关。肿瘤组织中 SMOX 表达阳性的患者表明总生存期较差（P = 0.008），无复发生存期较短（P = 0.002）。 SMOX 的敲低抑制了 HCC 细胞增殖，使细胞周期停滞在 S 期，并导致细胞凋亡增加。体内研究表明，抑制肝癌细胞中的 SMOX 可以显着抑制裸鼠肿瘤的生长。此外，我们发现 SMOX 可能通过调节磷脂酰肌醇 3'-激酶/蛋白激酶 B 信号通路发挥其功能。我们的数据表明，SMOX 上调可能是 HCC 中的一个关键癌基因，并可能作为 HCC 的一个有价值的预后标志物和潜在的治疗靶点。
Aim Methods The polyamine catabolic enzyme, spermine oxidase (SMOX) is upregulated in chronic inflammatory conditions and linked to increased reactive oxygen species and DNA damage in various forms of cancers. The present study aims to explore the expression pattern and biological function of SMOX in hepatocellular carcinoma (HCC). We used quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry to examine SMOX expression in four HCC cell lines and 120 HCC clinical samples, and the clinical significance of SMOX was analyzed. The biological function of SMOX on HCC cells was detected both in vitro and in vivo. Results ConclusionResults showed that SMOX was overexpressed in HCC cell lines and clinical HCC tissues. Moreover, SMOX expression levels were gradually increased in normal liver, chronic hepatitis, and HCC tissues. Increased SMOX expression was correlated with poor clinical features of HCC. Patients with positive SMOX expression in tumor tissues indicated worse overall survival (P = 0.008) and shorter relapse-free survival (P = 0.002). Knockdown of SMOX inhibited HCC cell proliferation, arrested cell cycle at S phase, and resulted in an increase of apoptosis. The in vivo study showed that inhibition of SMOX in HCC cells significantly repressed tumor growth in nude mice. Furthermore, we showed that SMOX might exert its function by regulating the phosphatidylinositol 3 '-kinase/protein kinase B signaling pathway. Our data indicated that SMOX upregulation could be a critical oncogene in HCC and might serve as a valuable prognostic marker and potential therapeutic target for HCC.