Lysyl Oxidase Is Predictive of Unfavorable Outcomes and Essential for Regulation of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma.
Lysyl Oxidase Is Predictive of Unfavorable Outcomes and Essential for Regulation of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma.
复制标题
赖氨酰氧化酶可预测不良结果，并且对于肝细胞癌中血管内皮生长因子的调节至关重要。
DOI：
10.1007/s10620-015-3734-5
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发表时间：
2015
影响因子：
3.1
通讯作者：
Zhao Yinnong
中科院分区：
文献类型：
--
作者：
Zhu Jiye;Huang Shan;Wu Guobin;Huang Chaoyuan;Li Xianjian;Chen Zhigang;Zhao Lei;Zhao Yinnong
赖氨酰氧化酶（Lysyl oxidase，LOX）在多种恶性肿瘤中高表达，并参与肿瘤的侵袭和转移。目的探讨LOX在肝细胞癌（HCC）中的确切作用及其与VEGF的相关性。方法采用定量逆转录聚合酶链反应（RT-PCR）和免疫组化方法检测LOX在HCC组织及癌旁组织中的表达水平。在体外研究LOX敲低对细胞增殖、迁移和侵袭的影响。LOX在VEGF的调节中的作用进一步表征在已经用转化生长因子β（TGF-β）.ResultsOur研究表明，LOX在HCC细胞系和组织中上调。LOX表达升高的HCC患者的无病生存期和总生存期相对较短。LOX的敲低降低了HCC细胞的增殖、迁移和侵袭。LOX与VEGF的表达呈正相关。经TGF-β处理后，LOX和VEGF水平均呈剂量依赖性上调。在LOX siRNA处理的细胞中，VEGF和磷酸化p38的水平显著降低，并且不能被TGF-β上调。p38 MAPK信号的抑制废除TGF-β-介导的VGEF的上调，但不影响LOX的expressions.ConclusionsLOX似乎是一个预测不太有利的结果，并可能通过p38 MAPK信号调节VEGF的表达。
BackgroundLysyl oxidase (LOX) is frequently overexpressed in a variety of malignancies and involved in tumor invasion and metastasis. Furthermore, it has been shown that LOX is closely related to vascular endothelial growth factor (VEGF).AimsIn this study, we aimed to investigate the exact role of LOX and the correlation between LOX and VEGF in hepatocellular carcinoma (HCC).MethodsThe expression levels of LOX in HCC tissue and adjacent noncancerous tissue were evaluated by quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis. The effect of LOX knockdown on cell proliferation, migration, and invasion was investigated in vitro. The role of LOX in the regulation of VEGF was further characterized in HCC cells that had been treated with transforming growth factor beta (TGF-β).ResultsOur study showed that LOX was up-regulated in HCC cell lines and tissue. HCC patients with elevated expression of LOX had relatively shorter disease-free survival and overall survival. Knockdown of LOX reduced the proliferation, migration, and invasion of HCC cells. Additionally, the expression level of LOX positively correlated with that of VEGF. After treatment with TGF-β, the levels of LOX and VEGF were both up-regulated in a dose-dependent manner. In the cells treated with siRNA of LOX, levels of VEGF and phosphorylated p38 were significantly decreased and could not be up-regulated by TGF-β. Inhibition of p38 MAPK signaling abrogated TGF-β-mediated up-regulation of VGEF but did not affect LOX expression.ConclusionsLOX appears to be a predictor of less favorable outcomes and may regulate the expression of VEGF via p38 MAPK signaling.