The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
The impact of 3'UTR variants on differential expression of candidate cancer susceptibility genes.
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DOI：
10.1371/journal.pone.0058609
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Toland AE
中科院分区：
文献类型：
--
作者：
Skeeles LE;Fleming JL;Mahler KL;Toland AE
调控区的变异被预测在常见疾病的疾病易感性中起重要作用。已显示映射到微小RNA（miRNA）结合位点的多态性破坏miRNA靶向基因的能力，从而导致差异mRNA和蛋白质表达。皮肤肿瘤易感性5（Skts 5）通过SPRET/远交F1回交在NIH/奥拉中被鉴定为赋予化学诱导的皮肤癌易感性的位点。为了确定定位于Skts 5基因3′非翻译区（3′UTR）中推定的miRNA结合位点的菌株之间的多态性是否影响表达，我们对该位点上候选基因的3′ UTR进行了系统评价。9个基因的3′ UTR多态性符合连锁数据，其中8个含有可能干扰或引入miRNA结合的多态性。Bcap 29、Dgkb、Hbp 1、Pik 3cg、Twistnb和Tspan 13这6个基因的3′ UTR对荧光素酶表达的影响存在差异，但似乎不受预测仅与两种亚型之一结合的评估miRNA的差异调节。评价了从符合不太严格标准的基因座中选择的另外四个基因的3′ UTR。Ifrd 1和Etv 1显示出差异，并包含预测破坏或创建miRNA结合位点的多态性，但在所测试的miRNA的调节方面没有显示出差异。总之，在易感和耐药小鼠品系之间具有推定功能变体的多个3′ UTR影响差异表达，而与预测的miRNA结合无关。
Variants in regulatory regions are predicted to play an important role in disease susceptibility of common diseases. Polymorphisms mapping to microRNA (miRNA) binding sites have been shown to disrupt the ability of miRNAs to target genes resulting in differential mRNA and protein expression. Skin tumor susceptibility 5 (Skts5) was identified as a locus conferring susceptibility to chemically-induced skin cancer in NIH/Ola by SPRET/Outbred F1 backcrosses. To determine if polymorphisms between the strains which mapped to putative miRNA binding sites in the 3′ untranslated region (3′UTR) of genes at Skts5 influenced expression, we conducted a systematic evaluation of 3′UTRs of candidate genes across this locus. Nine genes had polymorphisms in their 3′UTRs which fit the linkage data and eight of these contained polymorphisms suspected to interfere with or introduce miRNA binding. 3′UTRs of six genes, Bcap29, Dgkb, Hbp1, Pik3cg, Twistnb, and Tspan13 differentially affected luciferase expression, but did not appear to be differentially regulated by the evaluated miRNAs predicted to bind to only one of the two isoforms. 3′UTRs from four additional genes chosen from the locus that fit less stringent criteria were evaluated. Ifrd1 and Etv1 showed differences and contained polymorphisms predicted to disrupt or create miRNA binding sites but showed no difference in regulation by the miRNAs tested. In summary, multiple 3′UTRs with putative functional variants between susceptible and resistant strains of mice influenced differential expression independent of predicted miRNA binding.
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影响因子：
14.9
作者：
LAIRD, PW;ZIJDERVELD, A;BERNS, A
通讯作者：
BERNS, A
影响因子：
14.9
作者：
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影响因子：
2.7
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Landi, Stefano
影响因子：
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作者：
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通讯作者：
Weinberger, Daniel R.
影响因子：
7.5
作者：
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通讯作者：
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