GOLPH3 Overexpression is Closely Correlated with Poor Prognosis in Human Non-Small Cell Lung Cancer and Mediates its Metastasis Through Upregulating MMP-2 and MMP-9
GOLPH3 Overexpression is Closely Correlated with Poor Prognosis in Human Non-Small Cell Lung Cancer and Mediates its Metastasis Through Upregulating MMP-2 and MMP-9
复制标题
GOLPH3过表达与人非小细胞肺癌不良预后密切相关，并通过上调MMP-2和MMP-9介导其转移。
DOI：
10.1159/000369753
复制
发表时间：
2015-01-01
影响因子：
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通讯作者：
Wang, Lian-tang
中科院分区：
文献类型：
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作者：
Wang, Ran;Ke, Zun-fu;Wang, Lian-tang
背景/目的：高尔基体磷蛋白3（Golgi phosphoprotein 3，GOLPH 3）是一种新发现的在细胞生长调控中起重要作用的癌基因。最近的研究表明，GOLPH 3的过表达与乳腺癌和其他癌症的患者生存率和M分类相关。然而，GOLPH 3促进非小细胞肺癌（NSCLC）转移的机制以前尚未阐明，因此是这项工作的重点。研究方法：采用免疫组化（IHC）和Western blotting检测GOLPH 3蛋白表达水平，小干扰RNA（siRNA）和transwell实验检测GOLPH 3在细胞迁移和侵袭中的作用，实时荧光定量PCR检测GOLPH 3 mRNA表达水平。结果如下：GOLPH 3与NSCLC患者的临床分期（P=0.012）、T分期（P=0.002）和转移（M分期）（P=0.008）显著相关，与预后呈负相关。GOLPH 3的敲低显著抑制了NSCLC细胞系的迁移和侵袭能力，并下调了MMP-2和MMP-9的酶活性和蛋白水平。结论：GOLPH 3的表达水平与NSCLC的转移和预后有关，GOLPH 3通过调节MMP-2和MMP-9的蛋白水平介导NSCLC的转移。版权所有（C）2015 S. Karger AG，巴塞尔
Background/Aims: Golgi phosphoprotein 3 (GOLPH3) is a newly reported oncogene that plays a significant role in regulating cell growth. Recent research has shown that overexpression of GOLPH3 is correlated with patient survival and M classification in breast cancer and other cancers. However, the mechanisms by which GOLPH3 contributes to metastasis in non-small cell lung cancer (NSCLC) have not been previously clarified and are therefore the focus of this work. Methods: Immunohistochemistry (IHC) and western blotting analysis were performed to assess the GOLPH3 protein level, small interfering RNA (siRNA) and transwell assays were conducted to investigate the role of GOLPH3 in migration and invasion, and real-time PCR was performed to estimate the level of GOLPH3 mRNA expression. Results: GOLPH3 was significantly correlated with clinicopathological variables, such as the clinical stage (P=0.012), T classification (P=0.002) and metastasis (M classification) (P=0.008), in NSCLC patients and was negatively correlated with the prognosis. Knockdown of GOLPH3 significantly suppressed the migratory and invasive ability of NSCLC cell lines and downregulated the enzyme activity and protein levels of MMP-2 and MMP-9. Conclusions: The expression level of GOLPH3 is correlated with metastasis and prognosis in NSCLC, and GOLPH3 mediates metastasis by regulating the protein levels of MMP-2 and MMP-9 in vitro. Copyright (C) 2015 S. Karger AG, Basel