Evidence for the role of promoter methylation in the regulation of MMP-9 gene expression
Evidence for the role of promoter methylation in the regulation of MMP-9 gene expression
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DOI：
10.1016/s0006-291x(02)02283-0
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发表时间：
2002-10-04
影响因子：
3.1
通讯作者：
St-Pierre, Y
中科院分区：
文献类型：
--
作者：
Chicoine, É;Estève, PO;St-Pierre, Y
一些研究报道，MMP-9在淋巴瘤组织中的表达升高与肿瘤的分期、分级或预后相关。由于DNA甲基化模式对基因表达至关重要，因此使用基因组亚硫酸氢盐测序对一系列淋巴瘤细胞系进行详细的甲基化分析。我们发现MMP-9启动子甲基化水平与MMP-9表达水平呈负相关。用DNA甲基化抑制剂处理淋巴瘤细胞可降低MMP-9启动子甲基化并增加MMP-9信使RNA和蛋白质分泌。这种增加的表达被PMA增强，PMA是淋巴瘤细胞中MMP-9的已知刺激物。最后，使用体外甲基化MMP-9启动子构建体的实验证实了DNA甲基化对转录活性产生抑制的事实。因此，结果表明甲基化可能有助于MMP-9启动子的转录活性。(C)2002 Elsevier Science（美国）。All rights reserved.
Several studies have reported that elevated MMP-9 expression in lymphoma tissues correlated with tumor stage, grade, or prognosis. Because the DNA methylation pattern is critical for gene expression, detailed methylation analysis using genomic bisulfite sequencing was performed on a series of lymphoma cell lines. We found an inverse correlation between level of methylation of the MMP-9 promoter and the level of MMP-9 expression. Treating lymphoma cells with a DNA methylation inhibitor decreased MMP-9 promoter methylation and increased MMP-9 messenger RNA and protein secretion. This increased expression was potentiated by PMA, a known stimulus of MMP-9 in lymphoma cells. Finally, experiments using in vitro methylated MMP-9 promoter constructs confirmed the fact that DNA methylation exerts suppression on transcriptional activity. The results thus indicate that methylation may contribute to the transcriptional activity of the MMP-9 promoter. (C) 2002 Elsevier Science (USA). All rights reserved.