DNA methylation and histone H3-K9 modifications contribute to MUC17 expression
DNA methylation and histone H3-K9 modifications contribute to MUC17 expression
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DOI：
10.1093/glycob/cwq155
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发表时间：
2011-02-01
期刊：
影响因子：
4.3
通讯作者：
Yonezawa, Suguru
中科院分区：
文献类型：
--
作者：
Kitamoto, Sho;Yamada, Norishige;Yonezawa, Suguru
MUC 17糖蛋白是主要在消化道中表达的膜相关粘蛋白。MUC 17的表达与胰腺导管腺癌（PDAC）的恶性潜能相关。在本研究中，我们提供了第一个报告的MUG！7基因表达通过表观遗传调控如启动子甲基化、组蛋白修饰和microRNA（miRNA）表达。在转录起始位点附近，MUC 17阴性癌细胞系（例如PANC 1）的DNA甲基化水平高，而MUC 17阳性细胞（例如AsPC-1）的DNA甲基化水平低。组蛋白H3-K9（H3-K9）修饰状态也与MUC 17表达密切相关。我们的研究结果表明，DNA甲基化和组蛋白H3-K9修饰在MUC 17表达中起着关键作用。此外，在PDAC患者中观察到低甲基化状态。这表明MUC 17启动子的低甲基化状态可能是诊断PDAC的一种新的表观遗传标记。此外，miRNA芯片分析结果显示，存在5个潜在的候选miRNA。MUC 17也可能是通过靶向其mRNA的3 '-非翻译区的miRNA进行转录后调节的。了解MUC 17的表观遗传学变化对于癌症患者的致癌风险诊断和预后预测具有重要意义。
MUC17 glycoprotein is a membrane-associated mucin that is mainly expressed in the digestive tract. It has been suggested that MUC17 expression is correlated with the malignancy potential of pancreatic ductal adenocarcinomas (PDACs). In the present study, we provided the first report of the MUG! 7 gene expression through epigenetic regulation such as promoter methylation, histone modification and microRNA (miRNA) expression. Near the transcriptional start site, the DNA methylation level of MUC17-negative cancer cell lines (e.g. PANC1) was high, whereas that of MUC17-positive cells (e.g. AsPC-1) was low. Histone H3-K9 (H3-K9) modification status was also closely related to MUC17 expression. Our results indicate that DNA methylation and histone H3-K9 modification in the 5' flanking region play a critical role in MUC17 expression. Furthermore, the hypomethylation status was observed in patients with PDAC. This indicates that the hypomethylation status in the MUC17 promoter could be a novel epigenetic marker for the diagnosis of PDAC. In addition, the result of miRNA microarray analysis showed that five potential miRNA candidates existed. It is also possible that the MUC17 might be post-transcriptionally regulated by miRNA targeting to the 3'-untranslated region of its mRNA. These understandings of the epigenetic changes of MUC17 may be of importance for the diagnosis of carcinogenic risk and the prediction of outcomes for cancer patients.