Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
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DOI：
10.1371/journal.pone.0052624
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Howe PH
中科院分区：
文献类型：
--
作者：
Hussey GS;Link LA;Brown AS;Howley BV;Chaudhury A;Howe PH
人类癌症临床管理中的一个主要挑战是根据风险和有利反应的可能性准确地对患者进行分层。某些肿瘤类型的明显表型异质性使分层变得混乱，通常没有明显的细分标准。尽管进行了密集的转录阵列分析，但癌症特异性“签名基因”的识别和验证仍然难以捉摸，部分原因是转录组不能反映蛋白质组。与转录后调控事件相关的简化没有考虑到转录后调控事件引起的转录本之间相对表达的变化。我们先前已经证明，转化生长因子β通过调节hnRNP E1的磷酸化而导致两种转录物DAB2和ILEI的表达增加，从而在转录后调节上皮-间充质转化。使用包括表达谱分析和RIP芯片分析的全基因组组合方法，我们已经确定了一组在转化生长因子β介导的EMT过程中诱导的翻译调控的mRNAs。HnRNP E1的协同翻译调控构成了抑制相关EMT促进基因表达的转录后调节子，从而使细胞能够快速、协调地调节多个EMT促进基因。
A major challenge in the clinical management of human cancers is to accurately stratify patients according to risk and likelihood of a favorable response. Stratification is confounded by significant phenotypic heterogeneity in some tumor types, often without obvious criteria for subdivision. Despite intensive transcriptional array analyses, the identity and validation of cancer specific ‘signature genes’ remains elusive, partially because the transcriptome does not mirror the proteome. The simplification associated with transcriptomic profiling does not take into consideration changes in the relative expression among transcripts that arise due to post-transcriptional regulatory events. We have previously shown that TGFβ post-transcriptionally regulates epithelial-mesenchymal transition (EMT) by causing increased expression of two transcripts, Dab2 and ILEI, by modulating hnRNP E1 phosphorylation. Using a genome-wide combinatorial approach involving expression profiling and RIP-Chip analysis, we have identified a cohort of translationally regulated mRNAs that are induced during TGFβ-mediated EMT. Coordinated translational regulation by hnRNP E1 constitutes a post-transcriptional regulon inhibiting the expression of related EMT-facilitating genes, thus enabling the cell to rapidly and coordinately regulate multiple EMT-facilitating genes.
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影响因子：
7
作者：
Beyer, A;Hollunder, J;Wilhelm, T
通讯作者：
Wilhelm, T
DOI：
10.1093/bfgp/3.2.103
发表时间：
2004-08-01
期刊：
Briefings in Functional Genomics & Proteomics
影响因子：
--
作者：
Beilharz, Traude H.;Preiss, Thomas
通讯作者：
Preiss, Thomas
影响因子：
9.2
作者：
Merritt, Christopher;Rasoloson, Dominique;Ko, Darae;Seydoux, Geraldine
通讯作者：
Seydoux, Geraldine
影响因子：
13.8
作者：
Pradet-Balade, B;Boulmé, F;Garcia-Sanz, JA
通讯作者：
Garcia-Sanz, JA
影响因子：
--
作者：
Merrick, W C;Hensold, J O
通讯作者：
Hensold, J O