Grb2-associated binder 2 expression and its roles in uveal melanoma invasion.

Grb2-associated binder 2 expression and its roles in uveal melanoma invasion.
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Grb2相关binder 2表达及其在葡萄膜黑色素瘤侵袭中的作用

DOI:
10.3892/mmr.2017.7151
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发表时间:
2017-10
影响因子:
3.4
通讯作者:
Shi L
Shi L
中科院分区:
医学4区
文献类型:
--
作者:
Chen M;Li Y;Sun X;Zhang B;Li W;Wang S;Zhu X;Li F;Shi L

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葡萄膜黑色素瘤(UM)具有高转移和预后差的特点。进一步了解UM细胞的转移机制对于设计分子治疗是必不可少的。Grb2相关结合物2(Gab2)已被报道在各种类型的人类癌症的进展中起重要作用。然而,Gab2在UM迁移和侵袭中的作用仍不清楚。本研究旨在进一步评估Gab2在UM中的表达以及Gab2在UM细胞侵袭中的作用。临床UM组织样品和UM细胞系使用蛋白质印迹分析来分析Gab2的表达。利用RNA干扰技术研究Gab2对UM细胞迁移和侵袭特性的影响。Western blot法检测Gab2基因敲减组和对照组细胞中基质金属蛋白酶(MMP)2、MMP 9和fascin的表达水平。总共20个临床UM样品和UM细胞系的子集进行了研究,具有均匀的高Gab2表达。在体外实验中,使用小干扰RNA减少Gab2通过介导MMPs和fascin表达抑制UM细胞的迁移和侵袭。这些数据表明,Gab2是一个有用的预后指标UM和UM转移干预的新的治疗靶点。
Uveal melanoma (UM) is characterized by high metastasis and poor prognosis. A more improved understanding of the metastatic mechanism in UM cells is essential for the design of molecular therapy. Grb2-associated binder 2 (Gab2) has been reported to serve important roles in the progression of various types of human cancer. However, the role of Gab2 in the migration and invasion of UM remains unclear. The present study sought to further assess the expression of Gab2 in UM and the role of Gab2 in the invasion of UM cells. Clinical UM tissue samples and UM cell lines were analyzed using western blot analysis for the expression of Gab2. RNA interference was used to investigate the effect of Gab2 on the migratory and invasive characteristics of UM cells in vitro. The expression levels of matrix metalloproteinase (MMP)2, MMP9 and fascin in Gab2-knockdown, and control cells were also detected using western blot analysis. A total of 20 clinical UM samples and a subset of UM cell lines were investigated with uniformly high Gab2 expression. In the in vitro experiment, reduction of Gab2 using small interfering RNA inhibited the migration and invasion of UM cells by mediating MMPs, and fascin expression. These data suggest that Gab2 is a useful prognostic marker for UM and a novel therapeutic target for UM metastasis intervention.
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