Novel candidate targets of Wnt/β-catenin signaling in hepatoma cells
Novel candidate targets of Wnt/β-catenin signaling in hepatoma cells
复制标题
DOI：
10.1016/j.lfs.2006.10.024
复制
发表时间：
2007-01-23
期刊：
影响因子：
6.1
通讯作者：
Yeom, Young Il
中科院分区：
文献类型：
--
作者：
Lee, Heun-Sik;Park, Mee-Hee;Yeom, Young Il
β-连环蛋白/TCF 是 Writ 信号通路的关键组成部分，其活性在 HCC 中经常失调，导致基因激活，而这些基因的失调对肿瘤的发展具有重大影响。因此，鉴定 Writ 信号传导的靶基因对于理解 β-catenin 介导的致癌作用非常重要。我们使用代表 15,127 个独特的肝脏富集基因位点的 cDNA 微阵列分析了人肝癌细胞系的转录组谱，以确定 p-连环蛋白介导的转录的靶基因 (p < 0.005)。该分析产生了 130 个潜在的 Writ 相关分类基因，我们发现其中 33 个在假定的转录调控序列中包含共有的 TCF 结合位点。然后，在令状激活的实验模型中测试这些基因的令状依赖性表达。 PPL29、NEDD4L、FUT8、LYZ、STMN2、STARD7 和 KIAA0998 等基因被证明在 Wnt/β-catenin 激活后上调。对 33 个候选基因的基因本体分析表明存在与 Writ 通路相关的功能类别，例如细胞生长、增殖、粘附和信号转导。总之，我们鉴定了一些候选 Wnt/β-catenin 靶基因，可用于研究改变的 Writ 信号在肝癌发展中的作用，并表明其中一些可能是肝癌细胞中 Writ 信号的直接靶标。 (c) 2006 Elsevier Inc. 保留所有权利。
The activity of beta-catenin/TCF, the key component of Writ signaling pathway, is frequently deregulated in HCC, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Writ signaling is important for understanding beta-catenin-mediated carcinogenesis. We analyzed the transcriptome profile of human hepatoma cell lines using cDNA microarrays representing 15,127 unique, liver-enriched gene loci to identify the target genes of p-catenin-mediated transcription (p < 0.005). This analysis yielded 130 potential Writ-associated classifier genes, and we found 33 of them contain consensus TCF-binding sites in presumptive transcriptional regulatory sequences. These genes were, then, tested for their Writ-dependence of expression in experimental models of Writ activation. Genes such as PPL29, NEDD4L, FUT8, LYZ, STMN2, STARD7 and KIAA0998 were proven to be up-regulated upon Wnt/beta-catenin activation. Gene ontology analysis of the 33 candidate genes indicated the presence of functional categories relevant to Writ pathway such as cell growth, proliferation, adhesion and signal transduction. In conclusion, we identified a number of candidate Wnt/beta-catenin target genes that can be useful for studying the role of altered Writ signaling in liver cancer development, and showed that some of them might be direct targets of Writ signaling in hepatoma cells. (c) 2006 Elsevier Inc. All rights reserved.