DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis.
DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis.
复制标题
子宫内膜异位症在位子宫内膜COX-2基因启动子DNA低甲基化与其mRNA表达上调相关
DOI：
10.1186/2047-783x-17-12
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发表时间：
2012-05-18
影响因子：
4.2
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Wang D;Chen Q;Zhang C;Ren F;Li T
研究背景大量证据表明环氧合酶2（COX-2）在子宫内膜异位症的在位子宫内膜中过度表达，可能在子宫内膜异位症的发病机制中发挥重要作用。然而，目前很少有研究探讨子宫内膜异位症中COX-2异常高表达的分子机制。考虑到最近的一些研究表明DNA甲基化影响子宫内膜异位症的某些基因，因此本研究旨在确定子宫内膜异位症中观察到的COX-2高表达是否是由该基因启动子内的CpG岛低甲基化引起的。 方法收集60例子宫内膜异位症女性（子宫内膜异位症组）和20例非子宫内膜异位症女性（对照组）的子宫内膜组织。通过甲基化特异性PCR检查COX-2的甲基化状态。实时定量RT-PCR检测子宫内膜组织中COX-2 mRNA水平。结果子宫内膜异位症组在位子宫内膜COX-2启动子高甲基化频率(41.7%)低于对照组(75.0%),P< 0.05。子宫内膜异位症组在位子宫内膜COX-2 mRNA水平较对照组升高2.61倍（P< 0.01）。子宫内膜异位症组和对照组未甲基化子宫内膜中COX-2 mRNA水平分别高于同组甲基化子宫内膜的2.39倍和2.66倍（P< 0.01）。结论COX-2启动子内的低甲基化可能是子宫内膜异位症在位子宫内膜基因表达升高的原因。
BackgroundAccumulated evidence reveals that cyclooxygenase-2 (COX-2) was overexpressed in eutopic endometrium of endometriosis, which may play a critical role in the pathogenesis of endometriosis. However, few studies have been performed to explore the molecular mechanisms underlying the abnormal high expression of COX-2 in endometriosis. Considering the fact that a number of recent studies have shown DNA methylation affecting some genes in endometriosis, the present study was therefore aimed to determine whether the observed high expression COX-2 in endometriosis is caused by the hypomethylation of CpG island within the promoter of this gene.MethodsThe endometrial tissues were collected from 60 women with endometriosis (endometriosis group) and 20 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation specific PCR. Quantitative real-time RT-PCR was performed to measure COX-2 mRNA level in endometrial tissues.ResultsThe frequency of promoter hypermethylation of COX-2 was lower in eutopic endometrium of the endometriosis group (41.7%) than that in the control group (75.0%),P< 0.05. COX-2 mRNA level in the eutopic endometrium of the endometriosis group was 2.61-fold higher than that in the control group (P< 0.01). COX-2 mRNA level in unmethylated endometrium of the endometriosis group or the control group was 2.39-fold and 2.66-fold, respectively, higher than that in the methylated endometrium of the same group (P< 0.01).ConclusionsThe hypomethylation within the promoter of COX-2 may be responsible for the elevated gene expression in eutopic endometrium of endometriosis.