Regulation of COX-2 expression by miR-146a in lung cancer cells.
Regulation of COX-2 expression by miR-146a in lung cancer cells.
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DOI：
10.1261/rna.044149.113
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Lutz CS
中科院分区：
文献类型：
--
作者：
Cornett AL;Lutz CS
在本文中，作者描述了miR-146a在肺癌细胞中调控前列腺素生成所需的COX-2表达。这是通过miR-146a靶向3 ' UTR位点实现的，该位点存在于显示长3 ' UTR的COX-2 mrna中，但不存在于短COX-2 3 ' UTR中。他们报告了肺癌细胞中miR-146a水平和COX-2水平之间的负相关。这项工作导致了一个模型，即肺癌细胞中miR-146a的下调有助于COX-2的过表达，从而通过前列腺素合成增加细胞生长。前列腺素是一类介导细胞炎症反应和控制细胞生长的分子。花生四烯酸氧化转化为前列腺素H2是由环加氧酶COX-1和COX-2两种同工酶完成的。COX-1是组成性表达，而COX-2可被促炎细胞因子等外部刺激瞬时诱导。有趣的是，COX-2在包括肺癌在内的许多癌症中过度表达。MicroRNAs （miRNAs）是一种具有调节基因表达功能的小RNA分子。先前的研究暗示了mirna在人类癌症中的重要作用。我们在这里证明，与正常肺细胞相比，miR-146a在肺癌细胞中的表达水平显著降低。相反，肺癌细胞有更高水平的COX-2蛋白和mRNA表达。miR-146a的引入可以特异性地吞噬COX-2蛋白，并通过前列腺素生成测量COX-2的生物活性。miR-146a对COX-2的调控是通过存在于3 ' UTR中的单个mirna结合位点介导的。因此，我们认为miR-146a表达的降低有助于肺癌细胞中COX-2的上调和过表达。由于潜在的miRNA介导的调控是选择性多聚腺苷化位点选择的功能结果，了解调节COX-2 mRNA选择性多聚腺苷化和miRNA靶向的分子机制将使我们深入了解COX-2表达如何参与转移性疾病的发展。
In this paper, the authors describe the regulation of COX-2 expression, which is required for prostaglandin production, by miR-146a in lung cancer cells. This is achieved by miR-146a targeting a 3′ UTR site that is present in COX-2 mRNAs displaying long 3′ UTRs but is absent in short COX-2 3′ UTRs. They report an inverse correlation between miR-146a levels and COX-2 levels in lung cancer cells. This work leads to a model whereby miR-146a down-regulation in lung cancer cells contributes to the overexpression of COX-2 and therefore to increased cell growth through prostaglandin synthesis. Prostaglandins are a class of molecules that mediate cellular inflammatory responses and control cell growth. The oxidative conversion of arachidonic acid to prostaglandin H2 is carried out by two isozymes of cyclooxygenase, COX-1 and COX-2. COX-1 is constitutively expressed, while COX-2 can be transiently induced by external stimuli, such as pro-inflammatory cytokines. Interestingly, COX-2 is overexpressed in numerous cancers, including lung cancer. MicroRNAs (miRNAs) are small RNA molecules that function to regulate gene expression. Previous studies have implicated an important role for miRNAs in human cancer. We demonstrate here that miR-146a expression levels are significantly lower in lung cancer cells as compared with normal lung cells. Conversely, lung cancer cells have higher levels of COX-2 protein and mRNA expression. Introduction of miR-146a can specifically ablate COX-2 protein and the biological activity of COX-2 as measured by prostaglandin production. The regulation of COX-2 by miR-146a is mediated through a single miRNA-binding site present in the 3′ UTR. Therefore, we propose that decreased miR-146a expression contributes to the up-regulation and overexpression of COX-2 in lung cancer cells. Since potential miRNA-mediated regulation is a functional consequence of alternative polyadenylation site choice, understanding the molecular mechanisms that regulate COX-2 mRNA alternative polyadenylation and miRNA targeting will give us key insights into how COX-2 expression is involved in the development of a metastatic condition.
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影响因子：
4.8
作者：
Dixon, DA;Kaplan, CD;Prescott, SM
通讯作者：
Prescott, SM
DOI：
10.1073/pnas.0802682105
发表时间：
2008-05-20
影响因子：
11.1
作者：
Jazdzewski, Krystian;Murray, Elizabeth L.;de la Chapelle, Albert
通讯作者：
de la Chapelle, Albert
影响因子：
6.4
作者：
Liu, Xuhang;Fortin, Kristine;Mourelatos, Zissimos
通讯作者：
Mourelatos, Zissimos
DOI：
10.1016/s1357-2725(98)00152-6
发表时间：
1999-05-01
影响因子：
4
作者：
Hla, T;Bishop-Bailey, D;Trifan, OC
通讯作者：
Trifan, OC
DOI：
10.1158/1078-0432.ccr-08-1355
发表时间：
2009-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Liu X;Sempere LF;Galimberti F;Freemantle SJ;Black C;Dragnev KH;Ma Y;Fiering S;Memoli V;Li H;DiRenzo J;Korc M;Cole CN;Bak M;Kauppinen S;Dmitrovsky E
通讯作者：
Dmitrovsky E