Fatty-acid-binding protein 5 promotes cell proliferation and invasion in oral squamous cell carcinoma

Fatty-acid-binding protein 5 promotes cell proliferation and invasion in oral squamous cell carcinoma
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DOI:
10.1111/j.1600-0714.2009.00836.x
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发表时间:
2010-04-01
影响因子:
3.3
通讯作者:
Chen, Yuh-Ling
Chen, Yuh-Ling
中科院分区:
医学3区
文献类型:
--
作者:
Fang, Lei-Ya;Wong, Tung-Yiu;Chen, Yuh-Ling

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背景:口腔鳞状细胞癌(OSCC)是世界范围内最常见的恶性肿瘤之一,其发生的分子机制尚不清楚。我们先前的研究发现,脂肪酸结合蛋白5(FABP5)在口腔鳞状细胞癌中表达上调。FABP5过表达在口腔鳞癌进展中的意义尚未阐明。材料和方法:本研究利用重组腺相关病毒载体在人口腔鳞癌细胞系中表达并增加FABP5的表达。利用U6启动子驱动的短发夹状RNA(ShRNA)触发的RNA干扰来阻断FABP5基因的表达。应用Transwell Matrigel侵袭实验、MTS细胞增殖实验、逆转录-聚合酶链式反应、Western印迹和明胶酶谱分析等方法研究FABP5对口腔癌细胞侵袭、生长和基质金属蛋白酶(MMPs)产生的影响。结果:FABP5在口腔癌细胞中的过表达通过增加MMP9的表达促进细胞的增殖和侵袭。结论:本研究首次证明FABP5的表达调控了口腔癌细胞的侵袭行为和基质金属蛋白酶-9的产生,为口腔癌细胞的治疗干预提供了新的靶点。
Background:Oral squamous cell carcinoma (OSCC) is one of the most malignant neoplasms worldwide, and the molecular mechanism of oral tumorigenesis is still unclear. Fatty-acid-binding protein 5 (FABP5) was found in our previous study to be upregulated in oral squamous cell carcinomas by proteomic analysis. The implications of FABP5 overexpression in oral cancer progression have not yet been elucidated.Materials and methods:In this study, the recombinant adeno-associated virus vectors were used to deliver and increase the expression of FABP5 in human OSCC cell lines. U6 promoter-driven short-hairpin RNA (shRNA)-triggered RNA interference was used to block FABP5 gene expression. Transwell Matrigel invasion assay, MTS cell proliferation assay, reverse transcription-polymerase chain reaction, Western blot, and gelatin zymography analysis were used to investigate the effects of FABP5 on cell invasion, growth, and matrix metalloproteinase (MMP) production.Results:Overexpression of FABP5 in oral cancer cells increased cell proliferation and invasiveness by increasing the expression of MMP-9. Silencing FABP5 with shRNA significantly suppressed cell proliferation, MMP-9 activities, and invasiveness.Conclusion:Our study provides the first evidence that FABP5 expression modulated MMP-9 production and the invasive behavior of oral cancer cells and suggests that FABP5 may provide novel targets for therapeutic intervention.